Hindbrain induction and patterning during early vertebrate development

  • Dale Frank
  • Dalit Sela-Donenfeld


The hindbrain is a key relay hub of the central nervous system (CNS), linking the bilaterally symmetric half-sides of lower and upper CNS centers via an extensive network of neural pathways. Dedicated neural assemblies within the hindbrain control many physiological processes, including respiration, blood pressure, motor coordination and different sensations. During early development, the hindbrain forms metameric segmented units known as rhombomeres along the antero-posterior (AP) axis of the nervous system. These compartmentalized units are highly conserved during vertebrate evolution and act as the template for adult brainstem structure and function. TALE and HOX homeodomain family transcription factors play a key role in the initial induction of the hindbrain and its specification into rhombomeric cell fate identities along the AP axis. Signaling pathways, such as canonical-Wnt, FGF and retinoic acid, play multiple roles to initially induce the hindbrain and regulate Hox gene-family expression to control rhombomeric identity. Additional transcription factors including Krox20, Kreisler and others act both upstream and downstream to Hox genes, modulating their expression and protein activity. In this review, we will examine the earliest embryonic signaling pathways that induce the hindbrain and subsequent rhombomeric segmentation via Hox and other gene expression. We will examine how these signaling pathways and transcription factors interact to activate downstream targets that organize the segmented AP pattern of the embryonic vertebrate hindbrain.


Hindbrain Neural specification and patterning Hox proteins Meis and Pbx proteins FGF, Wnt and retinoic acid signaling Rhombomere patterning 



We wish to thank Dr. Yuval Peretz for his help with the illustrations. DF was supported by grants from the Israel Science Foundation (ISF, 658/15) and the Israel Cancer Research Fund (ICRF). DSD was supported by grants from the ISF (1515/16), The Chief Scientist Office of the Ministry of Health, Israel (3-0000-15441) and United States–Israel Binational Science Foundation (2015087).


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Biochemistry, Faculty of Medicine, The Rappaport Family Institute for Research in the Medical SciencesTechnion-Israel Institute of TechnologyHaifaIsrael
  2. 2.Koret School of Veterinary Medicine, The Robert H Smith Faculty of Agriculture, Food and EnvironmentThe Hebrew University of JerusalemRehovotIsrael

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