---
title: Evolution of the brain
disqus: hackmd
---
Evolution of the brain
===
:::success
> Documentation [name=MrDr.Staffan]
###### tags: `page`, `evolution`
:::

:::info
### Table of Contents
[TOC]
:::
[Top](#Table-of-Contents)

**Why this page?**
Because we don't Know. Or don't talk about it.

---

[[ I.e. we developed not from round worms but from corals.]]
700 Ma

# Notochord
By the age of 4, all notochord residue is replaced by a population of chondrocyte-like cells of unclear origin.[16]

# Calcium waves
Understanding calcium waves and sparks in central **neurons**
https://www.nature.com/articles/nrn3168

Intracellular Ca-carbonate biomineralization is widespread in cyanobacteria
https://www.pnas.org/doi/10.1073/pnas.1403510111

"Though the mechanisms of cyanobacterial calcification remain poorly understood, this process is invariably thought of as extracellular and the indirect by-product of metabolic activity. Here, we show that contrary to common belief, several cyanobacterial species perform Ca-carbonate biomineralizatioBefore o2n intracellularly. "

"We observed at least two phenotypes for intracellular biomineralization, one of which shows an original connection with cell division."

searched for intracellular Ca-carbonate inclusions in 68 cyanobacterial strains distributed throughout the phylogenetic tree of cyanobacteria

at least two distinct mechanisms of biomineralization: (i) one with Ca-carbonate inclusions scattered within the cell cytoplasm such as in Ca. G. lithophora, and (ii) another one observed in strains belonging to the Thermosynechococcus elongatus BP-1 lineage, in which Ca-carbonate inclusions lie at the cell poles.


[i wonder if Ca accumulation Before O2 was a problem. That it needed to be excreted.? ]

# Ciliate
https://en.wikipedia.org/wiki/Ciliate

# Sponges
[See calcium](https://hackmd.io/@sholmqvist/BJpKurTBB/%2FuAtidaIiS6qqdMBPI4CLNA)[This part needs to be condensed with the sponge part in calcium]

Evolving brains, Solid liquid synthetic.
https://www.youtube.com/live/EIb5-LJbcIM?si=H-Q-QlZpslmHKaH5

Syncytium of Cells. Calcium waves.
[Glass sponges' syncytia](https://en.wikipedia.org/wiki/Sponge#:~:text=Glass%20sponges%27%20syncytia)

The Significance of Syncytial Tissues for the Position of the Hexactinellida in the Metazoa
Hexactinellids (“glass sponges”)

https://en.wikipedia.org/wiki/Sponge_isolates

Model Systems for Exploring the Evolutionary Origins of the Nervous System
https://pubmed.ncbi.nlm.nih.gov/30083921/

## Sponge Moving without muscle.

Regulation of motility of cells from marine sponges by calcium ions
https://pubmed.ncbi.nlm.nih.gov/9023017/

predominantly the Ca2+ channels in plasma membrane control the level of [Ca2+]i.

Ionomycin - used to transport Ca2+ across membranes.

### sponge sneezing

https://youtu.be/-xczID7zeog?si=n55HYFVWQ3Lo6cjd

To remove clogs?

## Calcium in sponges
See calcium waves

## excavating sponges
pH Regulation and Tissue Coordination Pathways Promote Calcium Carbonate Bioerosion by Excavating Sponges
https://pubmed.ncbi.nlm.nih.gov/30679551/

[I.n. excavating fungi Functionalise low pH in excavating body parts.
these stratify these "tissues". The dead but coordinating cell in the middle. Within the organism a metabolic dead end for cells.]]

[[What happens to when those cells emerge a function.]]

Evolution of the mechanisms within a cell.

Molecular logic which is almost chemical and almost physical.
The metabolic emergence into 3D?

The black cosmos has no energy. Always a loss of electrons.

On earth we are at surplus of electrons right now? First it was reductive atmosphere?(refxxx)

Oxidation happened . Now we have 20-30% oxygen.

Since then oxygen is the Most Readily oxidized By providing electrons.

Yet it's all dance of electrons.

How reactive is oxygen?

what Is each Molecules rational. Overlapped.

# h1
Which of these six metals (Ca, Cu, Fe, Mg, Sn, or Zn) mosT


## Nutrients
Hexactinellide

subphylum Symplasma.

nutrient transport
Symplastic (between cytoplasm, plants)
(not Apoplastic Nutrient transport, like animals)

## cytoplasmic streaming
https://en.m.wikipedia.org/wiki/File:Cytoplasmic_streaming.webm

[jmfm. Hydration shells]

Release of Ca^2+^ from the
endoplasmic reticulum controls melanophore pigment aggregation (Thaler and
Haimo, 1992), and Ca^2+^ gradients cause local **solation of cytoplasm** leading to streaming in both Amoeba and the slime mold Physamm (Ridgeway and Durham,
1976; Jansen and Taylor, 1993).

pH and temperature

It is usually observed in large plant and animal cells, greater than approximately 0.1 mm[vague]. In smaller cells, the diffusion of molecules is more rapid, but diffusion slows as the size of the cell increases, so larger cells may need cytoplasmic streaming for efficient function.[1] (wiki)

In plant cells, chloroplasts may be moved around with the stream, possibly to a position of optimum light absorption for photosynthesis. The rate of motion is usually affected by light exposure, temperature, and pH levels

[this makes me think, hot mitochondria, I.e those Having to run hotter, will be transported away, these are more likely to produce glutamate.] if fuel is more difficult to melt. Old, stabilized that can't cool properly.

### Lyccasine & Dictyonal
[Something about phosphates In skeleton?

Seemingly there is a basic need of sequestering biominerals.

Are these the same as in the peroxisome cores? Do cyanobacteria have peroxisomes? ]

# cnidaria feeding

Surprisingly, the genes for the key enzymes for the synthesis of GABA and dopamine are expressed in epithelial cells (Figures 6J and S6B) instead of neurons. Moreover, both genes responded to satiety (Figures 6K and 6L) by either upregulation (dopamine) or downregulation (GABA).

[] (https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00538-2)

# Cnidaria (first real synapses)

[Comparison of Discharge Mechanisms of
Cnidarian Cnidae and Myxozoan Polar
Capsules](https://sci-hub.hkvisa.net/10.1080/10641260390244305)

**Ptychocyst**
Name derived from Greek ptychos meaning fold

[[Sure, but below lacks connection to Neurons.Neural nets.]]
Mariscal, Edwin J. Conklin and Charles H. Bigger (1977). [The Ptychocyst, a Major New Category of Cnida Used in Tube Construction by a Cerianthid Anemone](https://sci-hub.hkvisa.net/10.2307/1540427)

In the present study, the so-called atrichous isorhiza (i.e., atrich) involved in tube formation by a cerianthid anemone has been examined using a variety of microscopical methods.

Rather than being an atrich, this cnida represents an entirely new, major category of coelenterate organelle which has heretofore been undescribed

Contrary to all nematocysts and spirocysts studied to date, this new cnida is not helically folded within the capsule prior to discharge. Instead, it exhibits an entirely new method of folding of the undischarged thread resulting in a variable number of pleats in circumference, but entirely lacking pleats in length.

[Def.type of fold formed by doubling fabric back upon itself and securing it in place]

Brains are the development of skin. Skin represents the internal cell layer. Ectoderm.

Brains that expand their internal world, by making its skin as big as possible?

[Nemertea](https://en.wikipedia.org/wiki/Nemertea)
Nemertea is a phylum of animals also known as ribbon worms or proboscis worms

The outermost layer of the body has no cuticle, but consists of a ciliated and glandular epithelium containing rhabdites,[10] which form the mucus in which the cilia glide.[19] Each ciliated cell has many cilia and microvilli.[9]

# **Rhabdite** Fluid viscous reservoir?
"Slime production"
-or-
"What used to be an external cilial functiono of ectoderm".


2017 Biology OPEN
Slime production

Sulphated glycosaminoglycans support an assortment of planarian rhabdite structures

[1978 A new function of rhabdites: Mucus production for ciliary gliding](https://link.springer.com/article/10.1007/bf00999813)
[It is proposed that the principal function of rhabdites in the worms studied, is adhesion.](https://sci-hub.hkvisa.net/10.1007/BF00999813)

The rhabdite-forming cells on the ventral and ventro-lateral surfaces liebeneath a layer longitudinal muscles.
Various stages of synthesis are readilyseen although the later stages predominate. At first, the cell is dominated bya large, ovoid nucleus. In the scant cytoplasm only a few organelles, primarilymitochondria, are present. Figure 9 shows a cells, in a later stage, fixed while forming rhabdites.

Figure 1
[](https://link.springer.com/content/pdf/10.1007/BF00999813.pdf)

Figure 9
[![image](https://hackmd.io/_uploads/rkpar0hoA.png "Figure 9" =200x)](https://link.springer.com/content/pdf/10.1007/BF00999813.pdf)

[1967 Rhabdite Formation in Planaria: The Role of Microtubules](https://sci-hub.53yu.com/10.1016/S0022-5320(67)80024-8)

Observations:
Neoblasts or formative cells occur singly in the mesenchyme usually unassociated with other cellular elements (Fig. 1). They are round, oval, or irregular in profile and about 5um in diameter. The cytoplasm of these undifferentiated cells is characterized by an abundance of free ribosomes while other organelles are not prominent or few in number (Fig. 1)



Note the extensive rough-surfaced endoplasmic reticulum and large nucleolus (NI).

Golgi vesicles (arrows) contain a finely gramflar material of medium density

Gotgi vacuoles (Va) contain opaque granules in addition to the finely granular material

Fit. 4. Actively secreting rhabdite-forming gland cell.

The endoplasmic reticulum encloses the
extensive Golgi apparatus situated at the apex of the rbabdite (R)

Small smooth-surfaced vesicles
(V1) appear to be budding off from the rough-surfaced lamellae
The Golgi apparatus is composed
of vesicles (V2) containing material of medium density, a few membranous lamellae, and vacuoles
(Val) enclosing opaque granules. Microtubules (MT) parallel the rhabdite and extend toward the
Golgi apparatus. Small vesicles (V~) are located in close proximity to the microtubules and may fuse
with the limiting membrane of the rbabdite (V4). The striated capsule (C) of the rhabdite encloses the
opaque granules. Similar striations are present in one of the Golgi vacuoles (Va~).

1967
https://sci-hub.53yu.com/10.1016/S0022-5320(67)80024-8

1982
The Morphology of Turbellarian Rhabdites: Phylogenetic Implications
https://www.jstor.org/stable/3225810?seq=11

[2017 Sulphated glycosaminoglycans support an assortment of planarian rhabdite structures](https://journals.biologists.com/bio/article/6/5/571/962/Sulphated-glycosaminoglycans-support-an-assortment)

(B) Rhabdite undergoing expulsion from the surface


They are covered in cilia and use ciliary-gliding to traverse the substratum while hunting. Their body surface is covered in a layer of viscous slime primarily derived from specialised secretory granules known as rhabdites.

We show that these structures are rich in sulphated glycosaminoglycans (sGAGs). Most of these (269 of 285 examined) appear to be topologically closed spheroids that we name **ball-GAGs**.

Another class appears to burst to release flower- and star-like clusters which adhere to motile cilia

Rhabdites fall into two broad categories. One group are present in the outermost epidermal layer. These are sometimes termed ‘triclad-type’, ‘mucoid bodies’, or epithelial rhabdoids (Smith III et al., 1982). They are large (>5 µm before secretion and >15 µm afterwards) and are the subject of this paper (Fig. 1A-D). A second group are generated by cells in the inner, parenchymal cell layers and are released at the surface through tubular, microtubule-lined necks. These are smaller in size (0.4-0.7 µm), are often highly striated, and are sometimes referred to as ‘**adenal rhabdites**’ (Fig. 1E-H).

A further category comprises those rhabdites generated by the duo-gland adhesive and release system (Tyler, 1976, 1988; Whittington and Cribb, 2001). This fascinating organ is formed of a number of specialised cell types and forms a gland which facilitates transient adhesion by the secretion of adhesive glue (small 0.4-0.7 µm long rhabdites) and an agent that counteracts this adhesion. This type of gland can be identified by the presence of modified epithelial cells (anchor cells) and a crown of surrounding cilia.

[1997](https://link.springer.com/article/10.1023/A:1002934504296) Ultrastructural features of the epidermis of the planarian Artioposthia triangulata (Dendy)

## ball-GAGs

## 2024 Paper
https://link.springer.com/article/10.1007/s00441-024-03901-x

Visual organs in flatworms include two different types of photoreceptors, ciliated and rhabdomeric

1.
**Rhammite** glands have electron-dense, elongated granules of 0.2–0.6 mm diameter and 3.1–3.8 μm length (Fig. 2e); granules consist of a homogenous matrix surrounded by a membrane.

2.
**Rhabdite** glands resemble rhammite glands but have very long inclusions formed by an inner reticular matrix with electron-dense granules and a dense and concentric layered cortex (Fig. 2f).

3.
**Mucoid** glands are characterized by electron-lucent, spherical granules of 0.5 μm diameter. The matrix of the granules is filled with small, regularly spaced grains of higher density (Fig. 2g) and is enclosed in a membrane of irregular contour.

4.
**Aster-type glands** (Klauser and Tyler 1987) are filled with tightly packed, round granules whose matrix has a core of multiple, electron-dense, star-shaped grains (Fig. 2h). The cell membrane of aster-type glands further stands out by the lack of associated microtubules.

5.
**Perimaculate** glands (Klauser and Tyler 1987) also have tightly packed, ellipsoid granules with a moderately electron-dense matrix. Unlike aster-type glands, the matrix of these inclusions does not have dense grains in the core, but instead around the edges (Fig. 2i).

6.
**Buckle glands** have small spherical granules that are scattered throughout the cytoplasm more loosely compared to the glands mentioned above. Granules have an electron-dense periphery and are intersected by a dense cross bar, which gives them the shape of a belt buckle (Fig. 2j).

7.
**Vacuolated** glands show inclusions in the form of clear membrane-bound vesicles (“vacuoles”) of 0.1–0.3 μm diameter (Fig. 2k).

# A possible relative?
Cephalopharynx cannoni sp. nov.
(figures 2–7)
Description
Animals to 384 mm long and 192 mm wide with an oval body (figure 2). A tail is
never present. Body opaque with a glandular intestine. The entire epidermis is ciliated and may be partly syncytial. Epidermis height to 8 mm in section with cilia to 6 mm long. The distal edge of the epithelium is strongly eosinophilic.

Dermal and adenal rhabdites absent. Anterior kidney-shaped eyes present and consisting of numerous small (ca 1–2 mm) black pigment granules.

A lack of adenal or dermal rhabdites is an unusual condition in the family.
Several species of Typloplanidae lack dermal rhabdites (e.g. Adenoplea meridionalis
Kolasa, 1981) but few lack both types of inclusions, including species of Opistomum
Schmidt, 1848 and Pseudobockia Kolasa, 1981. The absence of rhammite tracts
might be interpreted as plesiomorphic based on their absence from species of
Dalyelliidae; however, the uncertain position of Typhloplanidae within the larger
phylogenetic framework, and the presence of rhabdites in other families of
Typhloplanoida (e.g. Promesostomidae, Trigonostomidae), may also be taken as
evidence of an independent loss in the new genus

# Eumetazoa
Proposed basal animal clade as a sister group of the Porifera (sponges).[5][6][7][8][9] - wiki

The competing hypothesis is the Myriazoa clade.


## Vesicle maturation
https://onlinelibrary.wiley.com/doi/10.1002/bies.201700024
UNC13B // MUNC13
idney cortical epithelial cells and is upregulated by hyperglycemia.

Studies in other species also indicate a role for this protein in the priming step of synaptic **vesicle exocytosis**.

Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia.

**Cript**
First appear in Fungi?
cytoskeletal anchoring of DLG4 in excitatory synapses

# Neoteny
What else do we know about the genetics of Neoteny? Inbreeding? "Domestication"

**Neoteny in nature?**

[Neoteny, Prolongation of Youth: From Naked Mole Rats to “Naked Apes” (Humans)](https://journals.physiology.org/doi/full/10.1152/physrev.00040.2015)

It has been suggested that highly social mammals, such as naked mole rats and humans, are long-lived due to neoteny (the prolongation of youth)

[2009 Transcriptional neoteny in the human brain](https://www.pnas.org/doi/10.1073/pnas.0900544106)

[IMO the tendency for neoteny is a likely consequence of improved access to a suitable niche/improved conditions, selective relaxation.][Especially in social/family forming species. as less work for resources would mean more time for raring offspring. This in essence reduces the extent and hence impact of selective pressures on the young.][An obvious situation would be that if the parents hunt less for food, they can be home protecting their young from predators. This would free-up or reduce the dependence on traits such as youth cammofluage.][this generally would concern traits that make the young independent.][This would have explanatory power over why human babies are particularily "helpless". and in psychological terms, why children need parental support to develop "normally".][naturally there would be a limit to such processes, such that the parents over protect the youth, making them dependent on the system also as adults. Perhaps this is why humans have such a propensity to display a range (depending on the parents choice of reering strategy). ]

**Neoteny in humans.**
Delbert D. Thiessen said that "neoteny becomes more apparent as early primates evolved into later forms" and that primates have been "evolving toward flat face."[23] Doug Jones argued that human evolution's trend toward neoteny may have been caused by sexual selection in human evolution for neotenous facial traits in women by men with the resulting neoteny in male faces being a "by-product" of sexual selection for neotenous female faces.[24]

[Transcriptional neoteny in the human brain](https://www.pnas.org/doi/10.1073/pnas.0900544106)
neotenic changes are present at the gene expression level. We show that the brain transcriptome is dramatically remodeled during postnatal development and that developmental changes in the human brain are indeed delayed relative to other primates. This delay is not uniform across the human transcriptome but affects a specific subset of genes that play a potential role in neural development.

# Positive selection.
Good stuff enable advantage (competitive, opens the niche.)
[This is what is happening when positive change. suddenly happens. I.e. Whale carcass in deep sea. Or finding a new food source?]

# Negative selection.
Removed beacase of bad stuff

The incidental purging of non-deleterious alleles due to such spatial proximity to deleterious alleles is called background selection.[4] This effect increases with lower mutation rate but decreases with higher recombination rate.

# X
You want offspring to grow up be fertile and contribute to group as soon as possible.

If there is excess, the parents will spend their time caring for offspring. This reduces the "need to develop into a "normal" adult. Basically all external forces driving an adult to become and adult.


# Humunculai




## blind mole=rats
*Spalacidae Spalacinae* // *Spalacinae mole-rats*
Q: Do these also live as long? ~20 years

Because they are completely blind, blind mole-rats have been important laboratory animals in tests on how eyes and eye proteins function. Although blind mole-rats have only atrophied subcutaneous eyes and are sightless, their circadian rhythm is kept. A few publications, such as Avivi et al., 2002, have proven that the circadian genes that control the biological clock are expressed in a similar manner as in sighted, above-ground mammals.[5]

## Big-headed African mole-rat // Giant molerat
*Tachyoryctes macrocephalus*

While the other mole rats not only live but also feed underground, this species mostly forages above ground, by digging a new tunnel to a patch of herbage.

MATING BEHAVIOR
POLYGYNY - male multiple females. "competition around males"

## naked mole rats
*Heterocephalus glaber*
10-30 years (in human care)

MATING BEHAVIOR
POLYANDRY - female multiple males "competition around females"

naked mole-rats, Heterocephalus glaber

Naked mole-rats are herbivores. They feed primarily on very large tubers (weighing as much as a thousand times the body weight of a typical mole-rat).

[So not a protein rich diet?]

A reduction in activity levels when the ambient temperature approaches the thermoneutral zone (TNZ) has also been reported for other species such as laboratory mice [41]. In social mole-rat species, the TNZ’s typically range between 28–36°C [6,29,32,42,43]. The TNZ of the highveld mole-rat is around 30–32°C [44], thus 30°C falls within this zone.

https://ncbi.nlm.nih.gov/pmc/articles/PMC5224861/#:~:text=In%20social%20mole-rat%20species,C%20falls%20within%20this%20zone.

### Thermoregulation
The naked mole-rat does not regulate its body temperature in typical mammalian fashion. They are thermoconformers rather than thermoregulators in that, unlike other mammals, body temperature tracks ambient temperatures. However, it has also been claimed that "the Naked Mole-Rat has a distinct temperature and activity rhythm that is not coupled to environmental conditions."[19]

The relationship between oxygen consumption and ambient temperature switches from a typical poikilothermic pattern to a homeothermic mode when temperature is at 29 °C or higher.[20]

[This means that they go from considerable variation in internal temp. to alternatively mainting a stable internal temperature, when the external is above 29dC. Could this also be the case for humans, but with a lower optimal temperature for stableness.]

[At low temperatures, at least I, need to move more in order to keep temperature up. In the other end of the spectrum, body is much more efficient in keeping temperatures not too high. ]

### Pain nociception?
The skin of naked mole-rats lacks neurotransmitters in their cutaneous sensory fibers.

[is this the same difference as seen in inbred humans win the north of sweden?]

### Mutation rates.

Naked mole rats have remained phenotypically unchanged for 30-50 Ma years. Since dinosaurs.

"Human primates might have Shifter toward cancer prone individuals to increase the variability in its offspring.

This is suggesting.. Men along with the notes on magnetic core//solar radiation /uv induced mutation//evolution of sex.
.. That life's first mission is to balance mutation rate to allow the variability needed for species adaptation.

If environment changes quickly. Then mutation rate also need to he high.

How can a cell control it's own mutation rate?

Chromatin packing?
Methylation? "Me-cytidine"?
Basking in the sun?

Mutation rate should be low if organism is well adapted.

On radioactive earth It would make sense if organisms had to fight mutations. That is protect it's internal structures/organisation from being ruined by mutations in its Critical parts.

That way, dna rna is a structure to protect from mutation. When the environment changes, I the organism struggles then they need to loosen their suppression of mutations to allow adaptation to happen.

Evolution on early earth was likely for the stability of systems, dna. DNA proved to be the most efficient way of protecting dna.

Before oxygen you have a sulfur, nitrogen and hydrocarbon, (co2) am world.

Click chemistry-like nitrogenation of Hydrocarbon chains
Nitrogen as the most common e- donor. [? ¿] (3 valence e-)

s acting as lubricant in these reactions. Since it binds stronger than N (Just as O has 2 valence e-)

However S is bigger and therefore weaker than O in its bindings.

Now nitrogen Is to being rid off, And everything is driven by oxidation of hydrocarbons.

[if This hypothesis is correct. Then This would give toward a solution of peto's paradoX]

cerebellum

# Released minks de-domestize and regrow brain size.

https://phys.org/news/2023-07-american-mink-regrow-brains-rare.amP

# Human vs chimpanzee
Promoter methylation is also associated with reduced gene expression, and comparison of human and chimpanzee liver, heart, and kidney tissues suggests that 12%–18% of the differential gene between these two species can be explained by differences in promoter methylation (Pai et al., 2011).

## Hammerhead sharks.

This is thanks to the special shape of that mad head, called a 'cephalofoil'. The cephalofoil helps the hammerhead shark to plane its way through a turn with more stability than the rest of sharks.

Är hajar en typisk art som länge haft överflöd av mat och den bästa taktiken.

Sådana arter fortbildar tills de 'flyter' ovanpå. Så långa som systemet tillåter.

Perfekt situation för emergent gene funKtion.
[brukar jag anse att naturen har en Riktning? Evolution säger att den är sLump.

Är det den frågan jag försöker koppla?

Determinism, mot reductionism. Och svaret är emergens. Liv som en emergensmaskin.

född ur stora antal exakt likhet. Lång tid.

"spandrel?"

Att spänning mellan två olika typer av massa alltid skapas Om stor skala. Deras kemiska strukturer samma pressade över tryck och värme.

GeotekmiskA. Vents. kärnreaktorer. Co2.

Är det det allt jag skriver om?
]

# Evolution of         The embryo

## Notochord
Develops dorsal to the gut tube and ventral to the neural tube.

The notochord secretes a protein called sonic hedgehog (SHH)


[](https://www.cureus.com/articles/39755-embryology-of-the-fascial-system#!/)
https://www.cureus.com/articles/39755-embryology-of-the-fascial-system#!/
:::info
Figure 1: A somite and its components
1: layer of cells from ectoderm that will develop epidermis; 2: neural tube; 3: epimere, part of myotome; 4: dermatome; 5: sclerotome; 6: hypomere, part of myotome; 7: celoma cavity; 8: somatopleure; 9: splancnopleure; 10: abdominal aorta; 11: notocord.
:::

Structure of mesoderm (middle layer) that forms before the neural fold.

It induces the neural fold invagination.

## Notochord secrets SHH
The notochord secretes a protein called sonic hedgehog (SHH)

SHH induces the neural groove


### SHH and Gli
[See Darling dogmas hypoxia](https://docs.google.com/spreadsheets/d/1VN1-DcHIccUT4tYZxjlY27uEdmUAc7zqnVCPuyU_ksc/edit#gid=1007787143&range=A54)

Graded SHH signaling is suggested to be mediated through the Gli family of proteins, which are vertebrate homologues of the Drosophila zinc-finger-containing transcription factor Cubitus interruptus (Ci). Ci is a crucial mediator of hedgehog (Hh) signaling in Drosophila.[55] In vertebrates, three different Gli proteins are present, viz. Gli1, Gli2 and Gli3, which are expressed in the neural tube.[56]

**Mice mutants for**:
**Gli1** show normal spinal cord development, suggesting that it is **dispensable(?)** for mediating SHH activity.[57]

**Gli2** mutant mice show abnormalities in the ventral spinal cord, with severe **defects in the floor plate** and ventral-most interneurons (V3).[58]

**Gli3** **antagonizes** SHH function in a dose-dependent manner, promoting dorsal neuronal subtypes.

## Chordate Sponges
A tunicate is a marine invertebrate animal, a member of the subphylum Tunicata (/ˌtjuːnɪˈkeɪtə/ TEW-nih-KAY-tə). It is part of the Chordata, a phylum which includes all animals with dorsal nerve cords and notochords (including vertebrates