Cerberus gene family

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The Cerberus gene family produces many different signal proteins that are antagonistically involved in establishing anterior-posterior patterning and left-right patterning in vertebrate embryos.[1]

Location[edit]

It is expressed in the anterior endoderm but can vary dorsally and ventrally between species. For example, in amphibians Cerberus is expressed in the anterior dorsal endoderm and in mice it is expressed in the anterior visceral endoderm.[2]

Anterior-Posterior patterning[edit]

Anterior-posterior patterning by Cerberus is accomplished by acting as an antagonist to nodal, bmp, and wnt signaling molecules in the anterior region of the vertebrate embryo during gastrulation. Knock down experiments in which Cerberus was partially repressed show a decreased formation of the head structures. In experiments where Cerberus was decreased and wnt, bmp and nodal signals were increased, embryos completely lacked head structures and develop only trunk structures. These experiments suggest that a balance of these signaling molecules is required for proper development of the anterior and posterior regions.[3]

Left-Right Asymmetry[edit]

Cerberus is also involved in establishing left-right asymmetry that is critical to the normal physiology of a vertebrate. By blocking nodal in the right side of the embryo, concentrations of nodal remain high only in the left side of the embryo and the nodal cascade cannot be activated in the right side. Because left-right asymmetry is so vital, Cerberus works along with the nodal cilia that push left-determining signal molecules to the left side of the embryo to ensure that the left-right axis is correctly established. Misexpression experiments show that lack of Cerberus expression on the right side can result in situs inversus and cardiovascular malformations.[4]

Heart Development[edit]

Cerberus plays a vital role in heart development and differentiation of cardiac mesoderm through activation of Nodal signaling molecule. Nodal and Wnt activity is antagonized in the endoderm which results in diffusible signals from Cerberus. More specifically, Nodal inhibits certain cells from joining cardiogenesis while simultaneously activating cells. The cells that respond to Nodal produce Cerberus in the underlying endoderm which causes heart development in adjacent cells. Knockdown experiments of Cerberus reduced endogenous cardiomyogenesis and ectopic heart induction.[5] The heart is developed asymmetrically using the left-right patterning induced by Cerberus which creates a higher concentration of signaling molecules on the left side. Experiments that inhibited Cerberus led to a loss of left-right polarity of the heart, which was shown by bilateral expression of left side-specific genes.[6]

References[edit]

  1. ^ Belo, Jose; Anna C. Silva, Ana-Cristina Borges, Mario Filipe, Margaret Bento, Lisa Goncalves, Marta Vitorino, Ana-Marisa Salguerio, Vera Texeira, Ana T. Tavares, Sara Marques (14 November 2008). "Generating asymmetries in the early vertebrate embryo: the role of the Cerberus-like family". Int. J. Dev. Biol. (53): 1399–1407. doi:10.1387/ijdb.072297jb. ISSN 1696-3547. 
  2. ^ Silva, A. C.; M. Filipe; K. Kuerner; H. Steinbeisser; J. A. Belo (15 Oct 2003). "Endogenous Cerberus activity is required for anterior head specification in Xenopus". Development: 4943–53. 
  3. ^ Tavares, A. T.; S. Andrade; A. C. Silvia; J. A. Belo (2007). "Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo.". Development 134 (11): 2051–60. doi:10.1242/dev.000901. PMID 17507406. 
  4. ^ Marszalek, J.; P. Ruiz-lozano; K. R. Chien; L.S. Goldstein (1999). "Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II.". Proc. Natl. Acad. Sci. U.S.A.: 5043–5048. doi:10.1073/pnas.96.9.5043. 
  5. ^ Foley, A. C.; O. Korol; A. M. Timmer; M. Mercola (1 Mar 2007). "Multiple functions of Cerberus cooperate to induce heart downstream of Nodal". Dev Biol (1): 57–65. 
  6. ^ Hashimoto, H.; M. Rebagliata; N. Ahmad; O. Muraoka; T. Kurokawa; M. Hibi; T. Suzuki (15 Apr 2004). "The Cerberus/Dan-family protein Charon is a negative regulator of Nodal signaling during left-right patterning in zebrafish". Development: 1741–53.