Mutations affecting neurogenesis and brain morphology in the zebrafish, Danio rerio

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 205-216 ◽  
Author(s):  
Y.J. Jiang ◽  
M. Brand ◽  
C.P. Heisenberg ◽  
D. Beuchle ◽  
M. Furutani-Seiki ◽  
...  

In a screen for embryonic mutants in the zebrafish a large number of mutants were isolated with abnormal brain morphology. We describe here 26 mutants in 13 complementation groups that show abnormal development of large regions of the brain. Early neurogenesis is affected in white tail (wit). During segmentation stages, homozygous wit embryos display an irregularly formed neural keel, particularly in the hindbrain. Using a variety of molecular markers, a severe increase in the number of various early differentiating neurons can be demonstrated. In contrast, late differentiating neurons, radial glial cells and some nonneural cell types, such as the neural crest-derived melanoblasts, are much reduced. Somitogenesis appears delayed. In addition, very reduced numbers of melanophores are present posterior to the mid-trunk. The wit phenotype is reminiscent of neurogenic mutants in Drosophila, such as Notch or Delta. In mutant parachute (pac) embryos the general organization of the hindbrain is disturbed and many rounded cells accumulate loosely in the hindbrain and midbrain ventricles. Mutants in a group of 6 genes, snakehead(snk), natter (nat), otter (ott), fullbrain (ful), viper (vip) and white snake (wis) develop collapsed brain ventricles, before showing signs of general degeneration. atlantis (atl), big head (bid), wicked brain (win), scabland (sbd) and eisspalte (ele) mutants have different malformation of the brain folds. Some of them have transient phenotypes, and mutant individuals may grow up to adults.

2019 ◽  
Vol 116 (25) ◽  
pp. 12494-12499 ◽  
Author(s):  
Gyu-Sang Hong ◽  
Sung Hoon Lee ◽  
Byeongjun Lee ◽  
Jae Hyouk Choi ◽  
Soo-Jin Oh ◽  
...  

Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia. Radial glial cells (RGCs), a type of neural stem cell in the ventricular zone, are essential for nurturing and delivering new immature neurons to the appropriate cortical target layers. Here we report that Anoctamin 1 (ANO1)/TMEM16A, a Ca2+-activated chloride channel, mediates the Ca2+-dependent process extension of RGCs. ANO1 is highly expressed and functionally active in RGCs of the mouse embryonic ventricular zone. Knockdown of ANO1 suppresses RGC process extension and protrusions, whereas ANO1 overexpression stimulates process extension. Among various trophic factors, brain-derived neurotrophic factor (BDNF) activates ANO1, which is required for BDNF-induced process extension in RGCs. More importantly, Ano1-deficient mice exhibited disrupted cortical layers and reduced cortical thickness. We thus conclude that the regulation of RGC process extension by ANO1 contributes to the normal formation of mouse embryonic brain.


2021 ◽  
pp. 1-26
Author(s):  
Tatsuro Yamamoto ◽  
Ayako Yamamoto ◽  
Hiroki Tanabe ◽  
Naomichi Nishimura

Abstract The brain is rich in long chain polyunsaturated fatty acids (PUFAs), which play an essential role in its development and functions. Here we examined the impact of maternal n-3 PUFA intake deficiency during gestation and lactation on the development of glial cells in the pup’s developing cerebral cortex. In addition, using myelination as indicator and the anti-myelin basic protein (MBP) as measurement to establish the relationship between the number of glial fibrillary acidic protein (GFAP)-positive cells and the development of oligodendrocytes, we determined the myelination state of the somatosensory cortex at day 14 postnatal. Rat dams were fed either a control (Cont) or an n-3 PUFA-deficient (Def) diet for 60 days (acclimatisation :14 days; gestation: 21 days; lactation:21 days). Pups lactated from dams throughout the experiment. The distribution pattern of astrocytes in pups on day 7 postnatal was immunohistochemically analysed using GFAP and brain lipid binding protein (BLBP) as markers for mature astrocytes and astrocyte-specific radial glial cells, respectively. It was observed that, when compared with Cont pups, GFAP-positive cells decreased, BLBP-positive cells increased and myelinated structures were sparser in the somatosensory cortices of Def pups. In the open field test on day 21 postnatal, behavioural parameters did not differ between groups. Our results indicated that inhibited maturation of astrocytes caused by maternal n-3 PUFA deficiency hindered the development of brain glial cells of neonatal rats and hence, maternal n-3 PUFA intake during the gestation and lactation periods may have been crucial for the brain cell composition of pups.


PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e44750 ◽  
Author(s):  
Shan-Ru Jeng ◽  
Wen-Shiun Yueh ◽  
Yi-Ting Pen ◽  
Marie-Madeleine Gueguen ◽  
Jérémy Pasquier ◽  
...  

Author(s):  
Yu-Hong Zhang ◽  
Mingrui Xu ◽  
Si Li ◽  
Haoda Wu ◽  
Xiang Shi ◽  
...  

AbstractThe hypothalamus contains an astounding heterogeneity of neurons to achieve its role in regulating endocrine, autonomic and behavioral functions. Despite previous progress in deciphering the gene regulatory programs linked to hypothalamus development, its molecular developmental trajectory and origin of neuronal diversity remain largely unknown. Here we combine transcriptomic profiling of 43,261 cells derived from Rax+ hypothalamic neuroepithelium with lineage tracing to map a developmental landscape of mouse hypothalamus and delineate the developmental trajectory of radial glial cells (RGCs), intermediate progenitor cells (IPCs), nascent neurons and peptidergic neurons in the lineage hierarchy. We show that RGCs adopt a conserved strategy for multipotential differentiation but generate both Ascl1+ and Neurog2+ IPCs, which display regionally differential origins in telencephalon. As transit-amplifying cells, Ascl1+ IPCs differ from their telencephalic counterpart by displaying fate bifurcation to produce both glutamatergic and GABAergic neurons. After classifying the developing neurons into 29 subtypes coded by diverse transcription factors, neurotransmitters and neuropeptides, we identified their molecular determinants via regulon analysis and further found that postmitotic neurons at nascent state possess the potential to resolve into more diverse subtypes of peptidergic neurons. Together, our study offers a single-cell framework for hypothalamus development and reveals that multiple cell types along the order of lineage hierarchy contribute to the fate diversification of hypothalamic neurons in a stepwise fashion, suggesting that a cascade diversifying model can deconstruct the origin of neuronal diversity.


Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5253-5263 ◽  
Author(s):  
P. Malatesta ◽  
E. Hartfuss ◽  
M. Gotz

The developing central nervous system of vertebrates contains an abundant cell type designated radial glial cells. These cells are known as guiding cables for migrating neurons, while their role as precursor cells is less clear. Since radial glial cells express a variety of astroglial characteristics and differentiate as astrocytes after completing their guidance function, they have been considered as part of the glial lineage. Using fluorescence-activated cell sorting, we show here that radial glial cells also are neuronal precursors and only later, after neurogenesis, do they shift towards an exclusive generation of astrocytes. These results thus demonstrate a novel function for radial glial cells, namely their ability to generate two major cell types found in the nervous system, neurons and astrocytes.


2010 ◽  
Vol 518 (24) ◽  
pp. 4855-4876 ◽  
Author(s):  
Nicolas Diotel ◽  
Colette Vaillant ◽  
Marie-Madeleine Gueguen ◽  
Svetlana Mironov ◽  
Isabelle Anglade ◽  
...  

2021 ◽  
Author(s):  
Leah Schembs ◽  
Ariane Willems ◽  
Kerstin Hasenpusch-Theil ◽  
James D Cooper ◽  
Katie Whiting ◽  
...  

Defects in primary cilia, cellular antennas that controls multiple intracellular signalling pathways, underlie several neurodevelopmental disorders, but how cilia control essential steps in human brain formation remains elusive. Here, we show that cilia are present on the apical surface of radial glial cells in human foetal forebrain. Interfering with cilia signalling in human organoids by mutating the INPP5E gene leads to the formation of ventral telencephalic cell types instead of cortical progenitors and neurons. INPP5E mutant organoids also showed increased SHH signalling and cyclopamine treatment partially rescued this ventralisation. In addition, ciliary expression of SMO was increased and the integrity of the transition zone was compromised. Overall, these findings establish the importance of primary cilia for dorsal/ventral patterning in human corticogenesis, indicate a tissue specific role of INPP5E as a negative regulator of SHH signalling and have implications for the emerging roles of cilia in the pathogenesis of neurodevelopmental disorders.


Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 165-178 ◽  
Author(s):  
A.F. Schier ◽  
S.C. Neuhauss ◽  
M. Harvey ◽  
J. Malicki ◽  
L. Solnica-Krezel ◽  
...  

In a large scale mutagenesis screen for embryonic mutants in zebrafish, we have identified 63 mutations in 24 loci affecting the morphogenesis of the zebrafish brain. The expression of marker genes and the integrity of the axonal scaffold have been studied to investigate abnormalities in regionalization, neurogenesis and axonogenesis in the brain. Mutants can be broadly classified into two groups, one affecting regionalization along the anterior-posterior or dorsal-ventral axis, and the other affecting general features of brain morphology. The first group includes one locus that is required to generate the anlage of the midbrain-hindbrain boundary region at the beginning of somitogenesis. Four loci were identified that affect dorsal-ventral patterning of the brain, including the previously described cyclops locus. Mutant embryos of this class show a reduction of ventral neuroectodermal structures and variable fusion of the eyes. The second group includes a large class of mutations affecting the formation of brain ventricles. Analysis of this class reveals the requirement of a functional cardiovascular system for ventricle enlargement during embryogenesis. Mutations in one locus lead to the formation of supernumerary primary neurons, a phenotype reminiscent of neurogenic mutants in Drosophila. Other mutant phenotypes described here range from abnormalities in the fasciculation and outgrowth of axons to defects in the diameter of the neural tube. The identified loci establish the genetic foundation for a further analysis of the development of the zebrafish embryonic brain.


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