Dorso-ventral and medio-lateral patterning in the hypothalamus

• Applicant: Dr. Gonzalo Alvarez-Bolado
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 166524758

The hypothalamus is a region of the brain responsible for the maintenance of the internal milieu and the energy balance of the organism. In addition, the lateral zone of the hypothalamus has a major role in the control of behavior. Hypothalamic developmental alterations can cause pathological conditions in the adult (like high blood pressure, obesity or sexual precocity). Due to the anatomical and functional complexity of the hypothalamus, however, its developmental mechanisms are still very mysterious. We have generated a conditional mouse mutant (Shh-cKO) specifically lacking expression of Sonic hedgehog (Shh) in thalamic and hypothalamic progenitor cells (1, 2). We showed that signalling protein Shh is crucial for lateral hypothalamic area specification. Since a key to the function of Shh in other brain regions is its interaction with transcription factor Gli3, we now hypothesize that 1) medial vs lateral hypothalamic patterning depends on a balance between Shh (lateralizing) and Gli3 (medializing); 2) removal of both Gli3 and Shh would reveal the role of other developmental genes in hypothalamic patterning. Therefore we propose 1) to analyze hypothalamic development in the available Gli3 null mutant mouse; 2) to analyze the hypothalamus of mice from crossings of the Gli3 mutant with our Shh-cKO; 3) to confirm and extend the data so obtained through loss-of-function experiments on wild type. This work will provide novel and essential information on the development of the lateral hypothalamic area.

• DFG Programme: Research Grants