A large amount of complex hormone associated processes occurring continuously in the human organism is necessary to maintain homeostasis in response to various internal and external conditions. In the same time, as the hormones use the bloodstream as their transmission medium, it is essential that their expression is strictly controlled to maintain their activity only when it is required. Because of that, the endocrine system evolved complex, self-regulating machinery that allows for precise signalling to the glands to initiate hormone expression, as well as equally quick negative feedback in the moment of reaching the optimal blood hormone concentration. The pituitary gland serves as the true endocrine part of that system, expressing a range of hormones that mostly serve as regulators of sub-systems serving different functions, scattered around organisms. The hypothalamus is the neuroendocrine part of the hypothalamic-pituitary axis, meaning it integrates the neuronal and hormonal signals, effectively linking the nervous and endocrine systems. The processes of hypothalamus and pituitary development share some significant similarities, which is unsurprising considering their close association and anatomical proximity at the base of the brain. Arising in highly overlapping developmental timeframes, they are both initially patterned by the gradients of extrinsic signalling molecules. After the initial lineage commitment, in both of those structures, intrinsic factors expressed by the distinct cell populations sustain the morphogenesis to result in a final complexly patterned structure. In this short review, the processes of the pituitary and hypothalamus development are described, with the most important factors driving them discussed.
9. Schally A V Arimura A Bowers CY Kastin AJ Sawano S Reeding TW. Hypothalamic neurohormones regulating anterior pituitary function. Recent Prog Horm Res. 1968;24:497–588.
10. Peters A Conrad M Hubold C Schweiger U Fischer B Fehm HL. The principle of homeostasis in the hypothalamus-pituitary-adrenal system: new insight from positive feedback. Am J Physiol Integr Comp Physiol. 2007; DOI:10.1152/ajpregu.00907.2006.
11. Markakis EA. Development of the neuroendocrine hypothalamus. Front Neuroendocrinol. 2002;23:257–91; DOI:10.1016/S0091-3022(02)00003-1.
12. Swanson LW. Brain maps 4.0-Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps. J Comp Neurol. 2018;526:935–43; DOI:10.1002/cne.24381.
13. Kobayashi D Kobayashi M Matsumoto K Ogura T Nakafuku Shimamura K. Early subdivisions in the neural plate define distinct competence for inductive signals. Development. 2002.
14. Braun MM. Wnt signaling is required at distinct stages of development for the induction of the posterior forebrain. Development. 2003; DOI:10.1242/dev.00685.
15. Lupo G Harris WA Lewis KE. Mechanisms of ventral patterning in the vertebrate nervous system. Nat Rev Neurosci. 2006;7:103–14; DOI:10.1038/nrn1843.
16. Strähle U Lam CS Ertzer R Rastegar S. Vertebrate floor-plate specification: variations on common themes. Trends Genet. 2004;20:155–62; DOI:10.1016/j.tig.2004.01.002.
17. Xie Y Dorsky RI. Development of the hypothalamus: conservation modification and innovation. Development. 2017;144:1588–99; DOI:10.1242/dev.139055.
18. Mathieu J Barth A Rosa FM Wilson SW Peyriéras N. Distinct and cooperative roles for Nodal and Hedgehog signals during hypothalamic development. Development. 2002.
19. Manning L Ohyama K Saeger B Hatano O Wilson SA Logan M Placzek M. Regional Morphogenesis in the Hypothalamus: A BMP-Tbx2 Pathway Coordinates Fate and Proliferation through Shh Downregulation. Dev Cell. 2006;11:873–85; DOI:10.1016/j.devcel.2006.09.021.
20. Zhao L Zevallos SE Rizzoti K Jeong Y Lovell-Badge R Epstein DJ. Disruption of SoxB1-Dependent Sonic hedgehog Expression in the Hypothalamus Causes Septo-optic Dysplasia. Dev Cell. 2012;22:585–96; DOI:10.1016/j.devcel.2011.12.023.
21. Lee JE Wu S-F Goering LM Dorsky RI. Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis. Development. 2006; DOI:10.1242/dev.02613.
22. Gaston-Massuet C McCabe MJ Scagliotti V Young RM Carreno G Gregory LC Jayakody SA Pozzi S Gualtieri A Basu B Koniordou M Wu C-I Bancalari RE Rahikkala E Veijola R Lopponen T Graziola F Turton J Signore M Mousavy Gharavy SN Charolidi N Sokol SY Andoniadou CL Wilson SW Merrill BJ Dattani MT Martinez-Barbera JP. Transcription factor 7-like 1 is involved in hypothalamo pituitary axis development in mice and humans. Proc Natl Acad Sci. 2016; DOI:10.1073/pnas.1503346113.
23. Rubenstein JLR Shimamura K Martinez S Puelles L. Regionalization of the prosencephalic neural plate. Annu Rev Neurosci. 1998;21:224–477; DOI:10.1146/annurev.neuro.21.1.445.
24. Sheng HZ Westphal H. Early steps in pituitary organogenesis. Trends Genet. 1999;15:236–40.
25. Gleiberman AS Fedtsova NG Rosenfeld MG. Tissue Interactions in the Induction of Anterior Pituitary: Role of the Ventral Diencephalon Mesenchyme and Notochord. Dev Biol. 1999;213:340–53; DOI:10.1006/DBIO.1999.9386.
26. Treier M Gleiberman AS O’Connell SM Szeto DP McMahon JA McMahon AP Rosenfeld MG. Multistep signaling requirements for pituitary organogenesis in vivo. Genes Dev. 1998;12:1691–704; DOI:10.1101/gad.12.11.1691.
27. Sheng HZ Zhadanov AB Mosinger B Fujii T Bertuzzi S Grinberg A Lee EJ Huang SP Mahon KA Westphal H. Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. Science. 1996;272:1004–7; DOI:10.1126/SCIENCE.272.5264.1004.
28. Treier M O’Connell S Gleiberman A Price J Szeto DP Burgess R Chuang PT McMahon AP Rosenfeld MG. Hedgehog signaling is required for pituitary gland development. Development. 2001;128.
29. Scully KM Rosenfeld MG. Pituitary development: Regulatory codes in mammalian organogenesis. Science (80- ). 2002; DOI:10.1126/science.1062736.
30. Ericson J Norlin S Jessell T Edlund T. Integrated FGF and BMP signaling controls the progression of progenitor cell differentiation and the emergence of pattern in the embryonic anterior pituitary. Development. 1998; DOI:10.1038/385257a0.
31. Lamolet B Pulichino AM Lamonerie T Gauthier Y Brue T Enjalbert A Drouin J. A pituitary cell-restricted T box factor Tpit activates POMC transcription in cooperation with Pitx homeoproteins. Cell. 2001;104:849–59.
32. Sornson MW Wu W Dasen JS Flynn SE Norman DJ O’Connell SM Gukovsky I Carrière C Ryan AK Miller AP Zuo L Gleiberman AS Andersen B Beamer WG Rosenfeld MG. Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature. 1996;384:327–33; DOI:10.1038/384327a0.
33. Smith ST Jaynes JB. A conserved region of engrailed shared among all en- gsc- Nk1- Nk2- and msh-class homeoproteins mediates active transcriptional repression in vivo. Development. 1996; DOI:10683172.
34. Dasen JS O’Connell SM Flynn SE Treier M Gleiberman AS Szeto DP Hooshmand F Aggarwal AK Rosenfeld MG. Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell. 1999;97:587–98.
35. Scully KM Jacobson EM Jepsen K Lunyak V Viadiu H Carrière C Rose DW Hooshmand F Aggarwal AK Rosenfeld MG. Allosteric effects of Pit-1 DNA sites on long-term repression in cell type specification. Science. 2000;290:1127–31; DOI:10.1126/SCIENCE.290.5494.1127.