ESPEYB15 1 Pituitary and Neuroendocrinology New mechanisms (6 abstracts)
1.6 Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors
Carreno G , Apps JR , Lodge EJ , Panousopoulos L , Haston S , Gonzalez-Meljem JM , Hahn H , Andoniadou CL & Martinez-Barbera JP
Developmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, UK
To read the full abstract: Development 2017;144:3289-3302
Aberrant development of the anterior pituitary can lead to congenital hypopituitarism (CH) in humans and hence understanding how this organ develops is critical to understand CH. The anterior pituitary develops in intimate contact with the prospective hypothalamus, which secretes growth factors that are required for the pituitary gland to grow. In this elegant paper, from Martinez-Barbera’s laboratory, they utilise a mouse transgenic line, Hesx1Cre/+ to either delete or activate Shh pathway, which is known be important for midline development. By deleting Shh from the anterior hypothalamus, the authors show that Shh signalling in this tissue is critical for Rathke’s pouch induction, hence dissecting out the role of this signalling during early development. Mutations in hSHH lead to holoprosencephaly, a severe middle defect that can been linked to congenital hypopituitarism. Indeed mutations in downstream effectors of SHH, such as GLI2, lead to CH with brain abnormalities in humans, demonstrating the clinical importance of components of this pathway in pituitary disease. How Shh activates or induces Lhx3/Lhx4 in pituitary precursors remains unknown, but this work clearly shows that it acts upstream of these factors. Therefore, Shh secreting molecules could also potentially be used in stem cell differentiation protocols to differentiate progenitor cells into Lhx3/Lhx4 RP progenitors.
Volume 15
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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