Talk:Neural - Tectum Development

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Cite this page: Hill, M.A. (2019, May 21) Embryology Neural - Tectum Development. Retrieved from


Dispersing movement of tangential neuronal migration in superficial layers of the developing chick optic tectum

Watanabe Y, Sakuma C & Yaginuma H. (2018). Dispersing movement of tangential neuronal migration in superficial layers of the developing chick optic tectum. Dev. Biol. , 437, 131-139. PMID: 29548944 DOI.

Watanabe Y1, Sakuma C2, Yaginuma H2. Author information Abstract During embryonic brain development, groups of particular neuronal cells migrate tangentially to participate in the formation of a laminated structure. Two distinct types of tangential migration in the middle and superficial layers have been reported in the development of the avian optic tectum. Here we show the dynamics of tangential cell movement in superficial layers of developing chick optic tectum. Confocal time-lapse microscopy in organotypic slice cultures and flat-mount cultures revealed that vigorous cell migration continued during E6.5-E13.5, where horizontally elongated superficial cells spread out tangentially. Motile cells exhibited exploratory behavior in reforming the branched leading processes to determine their pathway, and intersected with each other for dispersion. At the tectal peripheral border, the cells retraced or turned around to avoid protruding over the border. The tangentially migrating cells were eventually distributed in the outer stratum griseum et fibrosum superficiale and differentiated into neurons of various morphologies. These results revealed the cellular dynamics for widespread neuronal distribution in the superficial layers of the developing optic tectum, which underline a mode of novel tangential neuronal migration in the developing brain. KEYWORDS: Cell migration; Chick; Optic tectum; Time-lapse PMID: 29548944 DOI: 10.1016/j.ydbio.2018.03.010

Sonic Hedgehog Regulation of the Neural Precursor Cell Fate During Chicken Optic Tectum Development

Yang C, Li X, Li Q, Li H, Qiao L, Guo Z & Lin J. (2018). Sonic Hedgehog Regulation of the Neural Precursor Cell Fate During Chicken Optic Tectum Development. J. Mol. Neurosci. , 64, 287-299. PMID: 29285739 DOI.

Yang C1,2, Li X1, Li Q1, Li H3, Qiao L1,2, Guo Z2, Lin J4,5,6.

Abstract During nervous system development, neurons project axons over long distances to reach the appropriate targets for correct neural circuit formation. Sonic hedgehog (Shh) is a secreted protein and plays a key role in regulating vertebrate embryogenesis, especially in central nervous system (CNS) patterning, including neuronal migration and axonal projection in the brain and spinal cord. In the developing ventral midbrain, Shh is sufficient to specify a striped pattern of cell fates. Little is known about the molecular mechanisms underlying the Shh regulation of the neural precursor cell fate during the optic tectum development. Here, we aimed at studying how Shh might regulate chicken optic tectum patterning. In the present study, in ovo electroporation methods were employed to achieve the overexpression of Shh in the optic tectum during chicken embryo development. Besides, the study combined in ovo electroporation and neuron isolation culturing to study the function of Shh in vivo and in vitro. The fluorescent immunohistochemistry methods were used to check the related indicators. The results showed that Shh overexpression caused 87.8% of cells to be distributed to the stratum griseum central (SGC) layer, while only 39.3% of the GFP-transfected cells resided in the SGC layer in the control group. Shh overexpression also reduced the axon length in vivo and in vitro. In conclusion, we provide evidence that Shh regulates the neural precursor cell fate during chicken optic tectum development. Shh overexpression impairs neuronal migration and may affect the fate determination of transfected neurons. KEYWORDS: Cell fate; Chicken embryo; In ovo electroporation; Neural precursor cells; Optic tectum; Sonic hedgehog PMID: 29285739 DOI: 10.1007/s12031-017-1019-5


General Introduction to Drebrin

Shirao T & Sekino Y. (2017). General Introduction to Drebrin. Adv. Exp. Med. Biol. , 1006, 3-22. PMID: 28865011 DOI.

Shirao T1, Sekino Y2. Author information Abstract Drebrin was first discovered by our group as "developmentally regulated brain protein" from the chicken optic tectum. Drebrin is an actin-binding protein, which is classified into two major isoforms produced by alternative splicing from a single DBN1 gene. The isoform predominantly expressed in the adult brain (drebrin A) is neuron specific, containing a neuron-specific sequence (Ins2) in the middle of the molecule. Drebrin A is highly concentrated in dendritic spines, and its accumulation level is regulated by synaptic activity. In contrast, drebrin E, which lacks Ins2, is found in widespread but not ubiquitous cell types in various tissues. The isoform conversion from drebrin E to drebrin A occurs in parallel with synaptogenesis. Drebrin decorating F-actin is found at the recipient side of cell-cell communication systems, such as gap junctions, adherens junctions, immunological synapses, and neuronal synapses. In addition, it is involved in the cellular mechanisms of cell migration, cell process formation, cancer metastasis, and spermatogenesis. Lack of drebrin leads to the dysfunction of cell-cell communication, resulting in aberrant migration of metastatic cancer cells, aberrant synaptic function in dementia, and rupture of endothelial integrity. Because drebrin forms a unique F-actin with a longer helical crossover, drebrin may create an F-actin platform for molecular assembly and play a pivotal role in intercellular communication. KEYWORDS: Alternative splicing; Cancer; Cell migration; Intercellular communication; Physical property of actin filament; Synaptic plasticity; Synaptogenesis PMID: 28865011 DOI: 10.1007/978-4-431-56550-5_1


Thymosin β4 induces folding of the developing optic tectum in the chicken (Gallus domestics)

J Comp Neurol. 2012 Jun 1;520(8):1650-62. doi: 10.1002/cne.23004.

Wirsching HG, Kretz O, Morosan-Puopolo G, Chernogorova P, Theiss C, Brand-Saberi B. Source Department of Molecular Embryology, University of Freiburg, D-79104 Freiburg, Germany.


Thymosin β4 (Tβ4) is a highly conserved G-actin binding polypeptide with multiple intra- and extracellular functions. While stem-cell activation as well as promotion of cell survival and migration by Tβ4 have been investigated in various in vitro and in vivo studies, there are few data on the implications of Tβ4 in brain development. In the present study we analyzed Tβ4 expression in the developing optic tectum of the chicken (Gallus domesticus) and performed in ovo retroviral transduction and plasmid electroporation for overexpression and knockdown of Tβ4. We found marked Tβ4 expression in the tectal plate and in all neuronal layers of later developmental stages, but not in the ventricular zone where neural stem cells reside and divide. Knockdown of Tβ4 inhibited growth of Tβ4-depleted hemispheres, whereas overexpression of Tβ4 led to the production of neuroepithelial folds resembling gyri and sulci, which are not normally present in avian brains. The mechanism yielding enhanced growth of Tβ4 overexpressing hemispheres involved enhanced proliferation, thus indicating an impact of Tβ4 on the neural stem cell and/or progenitor cell population. In summary, we found that due to its effects on proliferation, Tβ4 expression has a large impact on neuroepithelial and macroscopic brain development. Copyright © 2011 Wiley Periodicals, Inc.

PMID 22120963

Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development

BMC Dev Biol. 2012 Mar 5;12:10.

Agoston Z, Li N, Haslinger A, Wizenmann A, Schulte D. Source Institute of Neurology (Edinger Institute), J, W, Goethe University Medical School, Heinrich Hoffmannstr, 7, 50628 Frankfurt, Germany.


BACKGROUND: During early stages of brain development, secreted molecules, components of intracellular signaling pathways and transcriptional regulators act in positive and negative feed-back or feed-forward loops at the mid-hindbrain boundary. These genetic interactions are of central importance for the specification and subsequent development of the adjacent mid- and hindbrain. Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced. RESULTS: Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, (ii) Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results extend our previous observation that Meis2 cooperates with Otx2 in tectal development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal anlage. CONCLUSION: The results described here suggest a model in which interdependent regulatory loops involving Pax3 and Pax7 in the dorsal mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7. PMID 22390724

Balancing of ephrin/Eph forward and reverse signaling as the driving force of adaptive topographic mapping

Development. 2012 Jan;139(2):335-45. Epub 2011 Dec 7.

Gebhardt C, Bastmeyer M, Weth F. Source Zoological Institute, Department of Cell- and Neurobiology, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.


The retinotectal projection, which topographically maps retinal axons onto the tectum of the midbrain, is an ideal model system with which to investigate the molecular genetics of embryonic brain wiring. Corroborating Sperry's seminal hypothesis, ephrin/Eph counter-gradients on both retina and tectum were found to represent matching chemospecificity markers. Intriguingly, however, it has never been possible to reconstitute topographically appropriate fiber growth in vitro with these cues. Moreover, experimentally derived molecular mechanisms have failed to provide explanations as to why the mapping adapts to grossly diverse targets in some experiments, while displaying strict point-to-point specificity in others. In vitro, ephrin-A/EphA forward, as well as reverse, signaling mediate differential repulsion to retinal fibers, instead of providing topographic guidance. We argue that those responses are indicative of ephrin-A and EphA being members of a guidance system that requires two counteracting cues per axis. Experimentally, we demonstrate by introducing novel double-cue stripe assays that the simultaneous presence of both cues indeed suffices to elicit topographically appropriate guidance. The peculiar mechanism, which uses forward and reverse signaling through a single receptor/ligand combination, entails fiber/fiber interactions. We therefore propose to extend Sperry's model to include ephrin-A/EphA-based fiber/fiber chemospecificity, eventually out-competing fiber/target interactions. By computational simulation, we show that our model is consistent with stripe assay results. More importantly, however, it not only accounts for classical in vivo evidence of point-to-point and adaptive topographic mapping, but also for the map duplication found in retinal EphA knock-in mice. Nonetheless, it is based on a single constraint of topographic growth cone navigation: the balancing of ephrin-A/EphA forward and reverse signalling.

PMID 22159582


Notch signalling stabilises boundary formation at the midbrain-hindbrain organiser

Development. 2011 Sep;138(17):3745-57. Epub 2011 Jul 27.

Tossell K, Kiecker C, Wizenmann A, Lang E, Irving C. Source Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.


The midbrain-hindbrain interface gives rise to a boundary of particular importance in CNS development as it forms a local signalling centre, the proper functioning of which is essential for the formation of tectum and cerebellum. Positioning of the mid-hindbrain boundary (MHB) within the neuroepithelium is dependent on the interface of Otx2 and Gbx2 expression domains, yet in the absence of either or both of these genes, organiser genes are still expressed, suggesting that other, as yet unknown mechanisms are also involved in MHB establishment. Here, we present evidence for a role for Notch signalling in stabilising cell lineage restriction and regulating organiser gene expression at the MHB. Experimental interference with Notch signalling in the chick embryo disrupts MHB formation, including downregulation of the organiser signal Fgf8. Ectopic activation of Notch signalling in cells of the anterior hindbrain results in an exclusion of those cells from rhombomeres 1 and 2, and in a simultaneous clustering along the anterior and posterior boundaries of this area, suggesting that Notch signalling influences cell sorting. These cells ectopically express the boundary marker Fgf3. In agreement with a role for Notch signalling in cell sorting, anterior hindbrain cells with activated Notch signalling segregate from normal cells in an aggregation assay. Finally, misexpression of the Notch modulator Lfng or the Notch ligand Ser1 across the MHB leads to a shift in boundary position and loss of restriction of Fgf8 to the MHB. We propose that differential Notch signalling stabilises the MHB through regulating cell sorting and specifying boundary cell fate. PMID 21795283 [PubMed - indexed for MEDLINE] PMCID: PMC3152928

The chick optic tectum developmental stages. A dynamic table based on temporal- and spatial-dependent histogenetic changes: A structural, morphometric and immunocytochemical analysis

J Morphol. 2011 Jun;272(6):675-97. doi: 10.1002/jmor.10943. Epub 2011 Apr 11.

Rapacioli M, Rodríguez Celín A, Duarte S, Ortalli AL, Di Napoli J, Teruel L, Sánchez V, Scicolone G, Flores V. Source Department of Biostructural Sciences, Interdisciplinary Group in Theoretical Biology, Favaloro University, Argentina.


Development is often described as temporal sequences of developmental stages (DSs). When tables of DS are defined exclusively in the time domain they cannot discriminate histogenetic differences between different positions along a spatial reference axis. We introduce a table of DSs for the developing chick optic tectum (OT) based on time- and space-dependent changes in quantitative morphometric parameters, qualitative histogenetic features and immunocytochemical pattern of several developmentally active molecules (Notch1, Hes5, NeuroD1, β-III-Tubulin, synaptotagmin-I and neurofilament-M). Seven DSs and four transitional stages were defined from ED2 to ED12, when the basic OT cortical organization is established, along a spatial developmental gradient axis extending between a zone of maximal and a zone of minimal development. The table of DSs reveals that DSs do not only progress as a function of time but also display a spatially organized propagation along the developmental gradient axis. The complex and dynamic character of the OT development is documented by the fact that several DSs are simultaneously present at any ED or any embryonic stage. The table of DSs allows interpreting how developmental cell behaviors are temporally and spatially organized and explains how different DSs appear as a function of both time and space. The table of DSs provides a reference system to characterize the OT corticogenesis and to reliably compare observations made in different specimens. Copyright © 2011 Wiley-Liss, Inc.

PMID 21484853


Early expression of axon guidance molecules in the embryonic chick mesencephalon and pretectum

Int J Dev Biol. 2010;54(4):743-53.

Riley KL, Gledhill S, Schubert FR. Source Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, UK.


Early axon tracts in the developing vertebrate brain are established along precise paths. Yet, little is known about axon guidance processes at early stages of rostral brain development. Using whole mount in situ hybridisation in combination with immunohistochemistry, we have analysed the expression patterns of Slits, Netrins, Semaphorins and the respective receptors during the formation of the early axon scaffold, particularly focusing on the pretectal-mesencephalic boundary. Many of these guidance molecules are expressed in close correlation with the growing tracts, and the nuclei of the corresponding neurons often express the respective receptors. The expression patterns of Slits and Netrins implicate them with the positioning of the longitudinal tracts along the dorsoventral axis, while Semaphorins could provide guidance at specific choice points. Our study provides a catalogue of gene expression for future studies on axon guidance mechanisms in the early brain.

PMID 19757387


The duration of Fgf8 isthmic organizer expression is key to patterning different tectal-isthmo-cerebellum structures

Development. 2009 Nov;136(21):3617-26. Epub 2009 Sep 30.

Sato T, Joyner AL. Source Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 511, New York, NY 10021, USA.


The isthmic organizer and its key effector molecule, fibroblast growth factor 8 (Fgf8), have been cornerstones in studies of how organizing centers differentially pattern tissues. Studies have implicated different levels of Fgf8 signaling from the mid/hindbrain boundary (isthmus) as being responsible for induction of different structures within the tectal-isthmo-cerebellum region. However, the role of Fgf8 signaling for different durations in patterning tissues has not been studied. To address this, we conditionally ablated Fgf8 in the isthmus and uncovered that prolonged expression of Fgf8 is required for the structures found progressively closer to the isthmus to form. We found that cell death cannot be the main factor accounting for the loss of brain structures near the isthmus, and instead demonstrate that tissue transformation underlies the observed phenotypes. We suggest that the remaining Fgf8 and Fgf17 signaling in our temporal Fgf8 conditional mutants is sufficient to ensure survival of most midbrain/hindbrain cells near the isthmus. One crucial role for sustained Fgf8 function is in repressing Otx2 in the hindbrain, thereby allowing the isthmus and cerebellum to form. A second requirement for sustained Fgf8 signaling is to induce formation of a posterior tectum. Finally, Fgf8 is also required to maintain the borders of expression of a number of key genes involved in tectal-isthmo-cerebellum development. Thus, the duration as well as the strength of Fgf8 signaling is key to patterning of the mid/hindbrain region. By extrapolation, the length of Fgf8 expression could be crucial to Fgf8 function in other embryonic organisers.

PMID 19793884