Rx3 and Shh direct anisotropic growth and specification in the zebrafish tuberal/anterior hypothalamus

Muthu, Victor; Eachus, Helen; Ellis, Pamela; Brown, Sarah Jane; Placzek, Marysia

doi:10.1242/dev.138305

Cited by 39 publications

(68 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar pathway was shown in chick, where Bmp2 and Bmp7 activate Tbx2, which represses Shh expression in the caudal hypothalamus (Manning et al, 2006). Shh expression may also be mediated by Rx3/Rax, as in both zebrafish rx3 and mouse Rax mutants, Shh expression is lost accompanied by a hypothalamic patterning defect (Muthu et al, 2016;Orquera et al, 2016). Interestingly, this phenotype is only observed when Rax is knocked out prior to embryonic day (E) 8.5 in mouse embryos, whereas a more specific defect in specification and differentiation of hypothalamic neurons is revealed when Rax is knocked out later (Lu et al, 2013;Orquera et al, 2016).…”

Section: Box 2 Modular Changes In Hypothalamic Anatomy: a Means To Ementioning

confidence: 54%

“…These signals establish discrete A/P zones (Kapsimali et al, 2004) and eventually help to define the boundaries of hypothalamic subregions ( Fig. 1B) (Muthu et al, 2016). The hypothalamus also has intrinsic dorsal/ventral (D/V) identity consistent with the alar, basal, and floor plate territories of the developing neural tube, and specific gene markers define these regions (Domínguez et al, 2011).…”

Section: Early Patterning Of the Hypothalamusmentioning

confidence: 99%

See 1 more Smart Citation

Development of the hypothalamus: conservation, modification and innovation

2017

View full text Add to dashboard Cite

The hypothalamus, which regulates fundamental aspects of physiological homeostasis and behavior, is a brain region that exhibits highly conserved anatomy across vertebrate species. Its development involves conserved basic mechanisms of induction and patterning, combined with a more plastic process of neuronal fate specification, to produce brain circuits that mediate physiology and behavior according to the needs of each species. Here, we review the factors involved in the induction, patterning and neuronal differentiation of the hypothalamus, highlighting recent evidence that illustrates how changes in Wnt/β-catenin signaling during development may lead to species-specific form and function of this important brain structure.

show abstract

Section: Box 2 Modular Changes In Hypothalamic Anatomy: a Means To Ementioning

confidence: 54%

Section: Early Patterning Of the Hypothalamusmentioning

confidence: 99%

Development of the hypothalamus: conservation, modification and innovation

2017

View full text Add to dashboard Cite

show abstract

“…We found that disc1 is expressed in the developing hypothalamus in proliferating progenitor cells that line the posterior part of the 3 rd ventricle and lateral recesses (45,51). Studies in mice have shown that in Disc1 mutants, progenitor cells in the cortex exit the cell cycle, and differentiate, prematurely (41).…”

Section: Discussionmentioning

confidence: 87%

Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function

Eachus

Bright

Cunliffe³

et al. 2017

Human Molecular Genetics

Self Cite

View full text Add to dashboard Cite

Psychiatric disorders arise due to an interplay of genetic and environmental factors, including stress. Studies in rodents have shown that mutants for Disrupted-In-Schizophrenia-1 (DISC1), a well-accepted genetic risk factor for mental illness, display abnormal behaviours in response to stress, but the mechanisms through which DISC1 affects stress responses remain poorly understood. Using two lines of zebrafish homozygous mutant for disc1, we investigated behaviour and functioning of the hypothalamic-pituitary-interrenal (HPI) axis, the fish equivalent of the hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that the role of DISC1 in stress responses is evolutionarily conserved and that DISC1 is essential for normal functioning of the HPI axis. Adult zebrafish homozygous mutant for disc1 show aberrant behavioural responses to stress. Our studies reveal that in the embryo, disc1 is expressed in neural progenitor cells of the hypothalamus, a conserved region of the vertebrate brain that centrally controls responses to environmental stressors. In disc1 mutant embryos, proliferating rx3+ hypothalamic progenitors are not maintained normally and neuronal differentiation is compromised: rx3-derived ff1b+ neurons, implicated in anxiety-related behaviours, and corticotrophin releasing hormone (crh) neurons, key regulators of the stress axis, develop abnormally, and rx3-derived pomc+ neurons are disorganised. Abnormal hypothalamic development is associated with dysfunctional behavioural and neuroendocrine stress responses. In contrast to wild type siblings, disc1 mutant larvae show altered crh levels, fail to upregulate cortisol levels when under stress and do not modulate shoal cohesion, indicative of abnormal social behaviour. These data indicate that disc1 is essential for normal development of the hypothalamus and for the correct functioning of the HPA/HPI axis.

show abstract

“…First, having initially acted as a morphogen to pattern the early hypothala- neurones of the tract of the post-optic commissure. 1,8,18,[27][28][29]36,44,45 However, future lineage-tracing studies that build on previous/recent studies 8,27,29,51 are needed to tease out which neurones require Shh non-autonomously vs autonomously; namely, to distinguish between neurones born from progenitors that respond to Shh (but do not express it) vs neurones that differentiate from Shh +ive progenitor populations.…”

Section: Anterior Progenitor Selection and Differentiationmentioning

confidence: 99%

Development of the basal hypothalamus through anisotropic growth

Pearson

Towers

et al. 2019

J Neuroendocrinology

Self Cite

View full text Add to dashboard Cite

The adult hypothalamus is subdivided into distinct domains: pre‐optic, anterior, tuberal and mammillary. Each domain harbours an array of neurones that act together to regulate homeostasis. The embryonic origins and the development of hypothalamic neurones, however, remain enigmatic. Here, we summarise recent studies in model organisms that challenge current views of hypothalamic development, which traditionally have attempted to map adult domains to correspondingly located embryonic domains. Instead, new studies indicate that hypothalamic neurones arise from progenitor cells that undergo anisotropic growth, expanding to a greater extent than other progenitors, and grow in different dimensions. We describe in particular how a multipotent Shh / Fgf10 ‐expressing progenitor population gives rise to progenitors throughout the basal hypothalamus that grow anisotropically and sequentially: first, a subset displaced rostrally give rise to anterior‐ventral/tuberal neuronal progenitors; then a subset displaced caudally give rise to mammillary neuronal progenitors; and, finally, a subset(s) displaced ventrally give rise to tuberal infundibular glial progenitors. As this occurs, stable populations of Shh +ive and Fgf10 +ive progenitors form. We describe current understanding of the mechanisms that induce Shh +ive /Fgf10 +ive progenitors and begin to direct their differentiation to anterior‐ventral/tuberal neuronal progenitors, mammillary neuronal progenitors and tuberal infundibular progenitors. Taken together, these studies suggest a new model for hypothalamic development that we term the “anisotropic growth model”. We discuss the implications of the model for understanding the origins of adult hypothalamic neurones.

show abstract

Rx3 and Shh direct anisotropic growth and specification in the zebrafish tuberal/anterior hypothalamus

Cited by 39 publications

References 65 publications

Development of the hypothalamus: conservation, modification and innovation

Development of the hypothalamus: conservation, modification and innovation

Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function

Development of the basal hypothalamus through anisotropic growth

Contact Info

Product

Resources

About