Limits...
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

The role of each Gli protein in the basal hypothalamus of the mouse. (A) Diagram showing expression domains of the Gli factors and Shh in the presumptive hypothalamus at the early, middle, and late phases. “lat” and “med,” lateral and medial domains, respectively (early phase according to Hui et al., 1994). (B) Summary diagrams of progenitor domains (neuroepithelium) of the basal hypothalamus in WT and mutants as deduced from phenotype analysis in the present study. (C) Diagrams comparable to those in (B) representing the progenitor domains in the spinal cord of WT and mutants as reported in the literature (as indicated). Question marks indicate that the V0/V1 domains have not been investigated. (D) Specific contribution of Gli proteins to the specification of the medial and lateral progenitor domains in three successive stages of development. Dotted square, possible influence of Gli2A on lateral progenitors before E8.5. The asterisk (∗) means that loss of GliA2 could be compensated by Gli3A. MBO, mamillary body. See Discussion for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4373379&req=5

Figure 11: The role of each Gli protein in the basal hypothalamus of the mouse. (A) Diagram showing expression domains of the Gli factors and Shh in the presumptive hypothalamus at the early, middle, and late phases. “lat” and “med,” lateral and medial domains, respectively (early phase according to Hui et al., 1994). (B) Summary diagrams of progenitor domains (neuroepithelium) of the basal hypothalamus in WT and mutants as deduced from phenotype analysis in the present study. (C) Diagrams comparable to those in (B) representing the progenitor domains in the spinal cord of WT and mutants as reported in the literature (as indicated). Question marks indicate that the V0/V1 domains have not been investigated. (D) Specific contribution of Gli proteins to the specification of the medial and lateral progenitor domains in three successive stages of development. Dotted square, possible influence of Gli2A on lateral progenitors before E8.5. The asterisk (∗) means that loss of GliA2 could be compensated by Gli3A. MBO, mamillary body. See Discussion for details.

Mentions: At E10.5 (late stage; Figure 3) the Gli expression pattern had changed again. While Gli2 expression was absent from the hypothalamic primordium (Figures 3G–I), Gli3 and Shh-activation diagnostic marker Gli1 showed overlapping expression domains in the medial domain (Figures 3A–C,M–O), suggesting a potential activator function of Gli3 (Gli3A) in the midline at this age. Shh was expressed in a lateral domain corresponding to the lateral progenitor domain (Alvarez-Bolado et al., 2012; neural Shh, lateral expression). We concluded that the hypothalamic expression of Shh and the Gli genes can be broadly subdivided into at least three stages (summarized in Figure 11A).


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)

The role of each Gli protein in the basal hypothalamus of the mouse. (A) Diagram showing expression domains of the Gli factors and Shh in the presumptive hypothalamus at the early, middle, and late phases. “lat” and “med,” lateral and medial domains, respectively (early phase according to Hui et al., 1994). (B) Summary diagrams of progenitor domains (neuroepithelium) of the basal hypothalamus in WT and mutants as deduced from phenotype analysis in the present study. (C) Diagrams comparable to those in (B) representing the progenitor domains in the spinal cord of WT and mutants as reported in the literature (as indicated). Question marks indicate that the V0/V1 domains have not been investigated. (D) Specific contribution of Gli proteins to the specification of the medial and lateral progenitor domains in three successive stages of development. Dotted square, possible influence of Gli2A on lateral progenitors before E8.5. The asterisk (∗) means that loss of GliA2 could be compensated by Gli3A. MBO, mamillary body. See Discussion for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 11: The role of each Gli protein in the basal hypothalamus of the mouse. (A) Diagram showing expression domains of the Gli factors and Shh in the presumptive hypothalamus at the early, middle, and late phases. “lat” and “med,” lateral and medial domains, respectively (early phase according to Hui et al., 1994). (B) Summary diagrams of progenitor domains (neuroepithelium) of the basal hypothalamus in WT and mutants as deduced from phenotype analysis in the present study. (C) Diagrams comparable to those in (B) representing the progenitor domains in the spinal cord of WT and mutants as reported in the literature (as indicated). Question marks indicate that the V0/V1 domains have not been investigated. (D) Specific contribution of Gli proteins to the specification of the medial and lateral progenitor domains in three successive stages of development. Dotted square, possible influence of Gli2A on lateral progenitors before E8.5. The asterisk (∗) means that loss of GliA2 could be compensated by Gli3A. MBO, mamillary body. See Discussion for details.
Mentions: At E10.5 (late stage; Figure 3) the Gli expression pattern had changed again. While Gli2 expression was absent from the hypothalamic primordium (Figures 3G–I), Gli3 and Shh-activation diagnostic marker Gli1 showed overlapping expression domains in the medial domain (Figures 3A–C,M–O), suggesting a potential activator function of Gli3 (Gli3A) in the midline at this age. Shh was expressed in a lateral domain corresponding to the lateral progenitor domain (Alvarez-Bolado et al., 2012; neural Shh, lateral expression). We concluded that the hypothalamic expression of Shh and the Gli genes can be broadly subdivided into at least three stages (summarized in Figure 11A).

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