Formation of the anterior neural plate

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R-HSA-9823739
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Pathway
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Homo sapiens
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5/5
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The neural plate is a thickened layer of cells on the dorsal surface of the gastrula rostral to the node and primitive streak. As development proceeds, the neural plate folds to form a tube that will generate the brain and spinal cord (reviewed in Massarwa et al. 2013). Failure to completely form a neural tube causes neural tube defects, such as spina bifida, which are the most common birth anomaly of the central nervous system (reviewed in Lee and Gleeson 2020). Though a single structure, the neural plate actually contains two regions formed from different progenitors and regulated by distinct gene expression programs: the anterior neural plate (ANP) gives rise to the forebrain and midbrain (reviewed in Wilson and Houart 2004, Kondoh et al. 2016) and the posterior neural plate (PNP) gives rise to the hindbrain and anterior part of the spinal cord (reviewed in Kondoh et al. 2016).
The ANP arises directly from the epiblast, requires inhibition of BMP signaling by secreted inhibitors from the anterior visceral endoderm (reviwed in Andoniadou and Martinez-Barbera 2013), and expresses SOX2 driven by OTX2, ZIC2, and POU5F1/POU3F1 bound to the N2 enhancer upstream of the SOX2 gene (inferred from mouse homologs in Iwafuchi-Doi et al. 2012). The posterior part of the PNP arises from neuromesodermal cells that express SOX2 driven by WNT and FGF acting through the N1 enhancer downstream of the SOX2 gene (inferred from mouse homologs in Takemoto et al. 2006).
Both the ANP and PNP express ZEB2 and SOX1, however the ANP is characterized by high OTX2 expression (Simeone et al. 1992), while the anterior PNP expresses higher levels of GBX2 (inferred from mouse homologs in Simeone et al. 1992). The boundary between the ANP and the PNP is partly determined by a mutual antagonism between OTX2 and GBX2. OTX2 from the ANP represses expression of GBX2 and GBX2 from the PNP represses expression of OTX2 (inferred from mouse homologs in Wassarman et al. 1997, Martinez‑Barbera et al. 2001, Li et al. 2001).
Literature References
PubMed ID Title Journal Year
9247335 Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function

Martinez, S, Rubenstein, JL, Wassarman, KM, Campbell, K, Joyner, AL, Martin, GR, Lewandoski, M

Development 1997
21185279 The Pou5f1/Pou3f-dependent but SoxB-independent regulation of conserved enhancer N2 initiates Sox2 expression during epiblast to neural plate stages in vertebrates

Takemoto, T, Uchikawa, M, Onichtchouk, D, Kondoh, H, Iwafuchi-Doi, M, Kamachi, Y, Leichsenring, M, Yoshida, Y, Driever, W

Dev Biol 2011
32423763 Closing in on Mechanisms of Open Neural Tube Defects

Gleeson, JG, Lee, S

Trends Neurosci 2020
22992956 Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells

Aruga, J, Matsuda, K, Kondoh, H, Niwa, H, Tesar, PJ, Iwafuchi-Doi, M, Murakami, K, Matsuo, I

Development 2012
27279156 Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate

Takemoto, T, Kondoh, H, Takada, S

Dev Growth Differ 2016
14960272 Early steps in the development of the forebrain

Wilson, SW, Houart, C

Dev Cell 2004
1353865 Nested expression domains of four homeobox genes in developing rostral brain

Boncinelli, E, Acampora, D, Stornaiuolo, A, Gulisano, M, Simeone, A

Nature 1992
11731459 Regionalisation of anterior neuroectoderm and its competence in responding to forebrain and midbrain inducing activities depend on mutual antagonism between OTX2 and GBX2

Schubert, F, Signore, M, Martinez-Barbera, JP, Lumsden, A, Puelles, E, Acampora, D, Gogoi, R, Boyl, PP, Simeone, A

Development 2001
11748135 Otx2 and Gbx2 are required for refinement and not induction of mid-hindbrain gene expression

Joyner, AL, Li, JY

Development 2001
23397132 Developmental mechanisms directing early anterior forebrain specification in vertebrates

Andoniadou, CL, Martinez-Barbera, JP

Cell Mol Life Sci 2013
16354715 Convergence of Wnt and FGF signals in the genesis of posterior neural plate through activation of the Sox2 enhancer N-1

Takemoto, T, Uchikawa, M, Kondoh, H, Kamachi, Y

Development 2006
24902834 Morphogenetic movements in the neural plate and neural tube: mouse

Ray, HJ, Massarwa, R, Niswander, L

Wiley Interdiscip Rev Dev Biol 2014
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