Homeobox-containing genes are thought to have a role in controlling development. In Drosophila, the engrailed (en) gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments. Different mutations in the mouse homologs, En1 and En2, produced different developmental defects that frequently are lethal. The human engrailed homologs 1 and 2 encode homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system.[2]
Engrailed (En) 1 is a homeobox gene that helps primarily regulate development in the dorsal midbrain and anterior hindbrain (cerebellum and colliculi) of humans. The expression of En1 is regulated until 13 days after fertilization by Fgf8, which controls the development of the forebrain and hindbrain. En1 is first expressed in this region on day 9.5 after fertilization for about 12 hours until En2 is expressed. After En2 expression, En1 is expressed again in other tissues such as somites and limb ectoderm throughout development.[3] A knockout mouse model with the En1 homeobox deleted was developed; mice died less than 24 hours after birth because they refused to feed, although they had the physical ability. The brains of the mice were studied and most of the cerebellum, colliculi, and cranial nerves 3 and 4 were missing. There was clear deletion in the mid-hindbrain, isthmus, junction region that began at day 9.5 after fertilization. All of the mice demonstrated marked forepaw deformities including fusion of digits and sixth digits. The 13th ribs and sternums displayed delayed and abnormal ossification. The mouse model demonstrated that the expression of En1 is critical in the correct development of the brain, limbs, and sternum.[4]
References
↑Kohler A, Logan C, Joyner AL, Muenke M (Mar 1993). "Regional assignment of the human homeobox-containing gene EN1 to chromosome 2q13-q21". Genomics. 15 (1): 233–235. doi:10.1006/geno.1993.1045. PMID8094370.
↑Wurst W, Auerbach AB, Joyner AL (July 1994). "Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum". Development. 120 (7): 2065–75. PMID7925010.
Further reading
Logan C, Hanks MC, Noble-Topham S, et al. (1993). "Cloning and sequence comparison of the mouse, human, and chicken engrailed genes reveal potential functional domains and regulatory regions". Dev. Genet. 13 (5): 345–358. doi:10.1002/dvg.1020130505. PMID1363401.
Logan C, Willard HF, Rommens JM, Joyner AL (1989). "Chromosomal localization of the human homeo box-containing genes, EN1 and EN2". Genomics. 4 (2): 206–209. doi:10.1016/0888-7543(89)90301-7. PMID2567700.
Loomis CA, Harris E, Michaud J, et al. (1996). "The mouse Engrailed-1 gene and ventral limb patterning". Nature. 382 (6589): 360–363. doi:10.1038/382360a0. PMID8684466.
Joliot A, Trembleau A, Raposo G, et al. (1997). "Association of Engrailed homeoproteins with vesicles presenting caveolae-like properties". Development. 124 (10): 1865–75. PMID9169834.
Mikkola I, Bruun JA, Holm T, Johansen T (2001). "Superactivation of Pax6-mediated transactivation from paired domain-binding sites by dna-independent recruitment of different homeodomain proteins". J. Biol. Chem. 276 (6): 4109–4118. doi:10.1074/jbc.M008882200. PMID11069920.
Schaefer LK, Wang S, Schaefer TS (2001). "Functional interaction of Jun and homeodomain proteins". J. Biol. Chem. 276 (46): 43074–43082. doi:10.1074/jbc.M102552200. PMID11551904.
Atit R, Sgaier SK, Mohamed OA, et al. (2006). "Beta-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse". Dev. Biol. 296 (1): 164–176. doi:10.1016/j.ydbio.2006.04.449. PMID16730693.
