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Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus.

Haddad-Tóvolli R, Paul FA, Zhang Y, Zhou X, Theil T, Puelles L, Blaess S, Alvarez-Bolado G - Front Neuroanat (2015)

Bottom Line: The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation.Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions.Our data confirm the model and are explained by it.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Cell Biology and Neuroanatomy, University of Heidelberg Heidelberg, Germany.

ABSTRACT
Secreted protein Sonic hedgehog (Shh) ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR) of transcription factors Gli2 and Gli3. This balance-the Shh-Gli code-is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e., we wanted to approach the question of a possible hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: (1) hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; (2) another source of diversity are differential requirements for Shh of neural vs. non-neural origin; (3) the medial progenitor domain known to depend on Gli2 for its development generates several essential hypothalamic nuclei plus the pituitary and median eminence; (4) the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

No MeSH data available.


Related in: MedlinePlus

Gli3 activator is dispensable for specification of the basal hypothalamus. (A–L)In situ detection of tuberal marker genes on E18.5 mouse brain sections, markers and genotypes as indicated. Black arrows indicate the arcuate nucleus. Black arrows in L indicate the ventromedial nucleus. (M–O)In situ detection of mamillary marker gene Lhx1 on E18.5 mouse brain sections, genotypes as indicated. Black arrows indicate the mamillary body (MBO). Arc, arcuate nucleus; MBO, mamillary body; VMH, ventromedial nucleus. Scale bars 500 μm.
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Figure 8: Gli3 activator is dispensable for specification of the basal hypothalamus. (A–L)In situ detection of tuberal marker genes on E18.5 mouse brain sections, markers and genotypes as indicated. Black arrows indicate the arcuate nucleus. Black arrows in L indicate the ventromedial nucleus. (M–O)In situ detection of mamillary marker gene Lhx1 on E18.5 mouse brain sections, genotypes as indicated. Black arrows indicate the mamillary body (MBO). Arc, arcuate nucleus; MBO, mamillary body; VMH, ventromedial nucleus. Scale bars 500 μm.

Mentions: We went on to analyze the developing Gli3Xt-J/Xt-J basal hypothalamus. At E18.5, expression of specific marker genes Npy, Pomc and SF-1 in the tuberal region (Figures 8A–F) and of Lhx1 in the mamillary region (Figures 8M,N), showed that a Gli3A function in presence of Gli2A is dispensable for the specification of the basal hypothalamus.


Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus.

Haddad-Tóvolli R, Paul FA, Zhang Y, Zhou X, Theil T, Puelles L, Blaess S, Alvarez-Bolado G - Front Neuroanat (2015)

Gli3 activator is dispensable for specification of the basal hypothalamus. (A–L)In situ detection of tuberal marker genes on E18.5 mouse brain sections, markers and genotypes as indicated. Black arrows indicate the arcuate nucleus. Black arrows in L indicate the ventromedial nucleus. (M–O)In situ detection of mamillary marker gene Lhx1 on E18.5 mouse brain sections, genotypes as indicated. Black arrows indicate the mamillary body (MBO). Arc, arcuate nucleus; MBO, mamillary body; VMH, ventromedial nucleus. Scale bars 500 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4373379&req=5

Figure 8: Gli3 activator is dispensable for specification of the basal hypothalamus. (A–L)In situ detection of tuberal marker genes on E18.5 mouse brain sections, markers and genotypes as indicated. Black arrows indicate the arcuate nucleus. Black arrows in L indicate the ventromedial nucleus. (M–O)In situ detection of mamillary marker gene Lhx1 on E18.5 mouse brain sections, genotypes as indicated. Black arrows indicate the mamillary body (MBO). Arc, arcuate nucleus; MBO, mamillary body; VMH, ventromedial nucleus. Scale bars 500 μm.
Mentions: We went on to analyze the developing Gli3Xt-J/Xt-J basal hypothalamus. At E18.5, expression of specific marker genes Npy, Pomc and SF-1 in the tuberal region (Figures 8A–F) and of Lhx1 in the mamillary region (Figures 8M,N), showed that a Gli3A function in presence of Gli2A is dispensable for the specification of the basal hypothalamus.

Bottom Line: The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation.Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions.Our data confirm the model and are explained by it.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Cell Biology and Neuroanatomy, University of Heidelberg Heidelberg, Germany.

ABSTRACT
Secreted protein Sonic hedgehog (Shh) ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR) of transcription factors Gli2 and Gli3. This balance-the Shh-Gli code-is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e., we wanted to approach the question of a possible hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: (1) hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; (2) another source of diversity are differential requirements for Shh of neural vs. non-neural origin; (3) the medial progenitor domain known to depend on Gli2 for its development generates several essential hypothalamic nuclei plus the pituitary and median eminence; (4) the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

No MeSH data available.


Related in: MedlinePlus