PMID- 7600984 OWN - NLM STAT- MEDLINE DCOM- 19950810 LR - 20220215 IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 121 IP - 6 DP - 1995 Jun TI - TGF alpha can act as a chemoattractant to perioptic mesenchymal cells in developing mouse eyes. PG - 1669-80 AB - Growth factors are believed to play an important role in regulating cell fate and cell behavior during embryonic development. Transforming growth factor alpha (TGF alpha), a member of the epidermal growth factor (EGF) superfamily, is a small polypeptide growth factor. Upon binding to its receptor, the EGF receptor (EGFR), TGF alpha can exert diverse biological activities, such as induction of cell proliferation or differentiation. To explore the possibility that TGF alpha might regulate cell fate during murine eye development, we generated transgenic mice that express human TGF alpha in the lens under the control of the mouse alpha A-crystallin promoter. The transgenic mice displayed multiple eye defects, including corneal opacities, cataracts and microphthalmia. At early embryonic stages TGF alpha induced the perioptic mesenchymal cells to migrate abnormally into the eye and accumulate around the lens. In situ hybridization revealed that the EGFR mRNA is highly expressed in the perioptic mesenchyme, suggesting that the migratory response is mediated by receptor activation. In order to test this model, the TGF alpha transgenic mice were bred to EGFR mutant waved-2 (wa-2) mice. We found that the eye defects of the TGF alpha transgenic mice are significantly abated in the wa-2 homozygote background. Because the EGFR mutation in the wa-2 mice is located in the receptor kinase domain, this result indicates that the receptor tyrosine kinase activity is critical for signaling the migratory response. Taken together, our studies demonstrate that TGF alpha is capable of altering the migratory decisions and behavior of perioptic mesenchyme during eye development. FAU - Reneker, L W AU - Reneker LW AD - Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA. FAU - Silversides, D W AU - Silversides DW FAU - Patel, K AU - Patel K FAU - Overbeek, P A AU - Overbeek PA LA - eng GR - EY-06578/EY/NEI NIH HHS/United States GR - EY-10448/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (Chemotactic Factors) RN - 0 (DNA Primers) RN - 0 (Transforming Growth Factor alpha) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Animals MH - Base Sequence MH - Cell Movement MH - *Chemotactic Factors MH - DNA Primers/genetics MH - ErbB Receptors/metabolism MH - Eye/anatomy & histology/*embryology MH - In Situ Hybridization MH - Lens, Crystalline/embryology MH - Mesoderm/*cytology MH - Mice MH - Mice, Transgenic MH - Molecular Sequence Data MH - Morphogenesis MH - Phenotype MH - Polymerase Chain Reaction MH - Transforming Growth Factor alpha/metabolism/*physiology EDAT- 1995/06/01 00:00 MHDA- 1995/06/01 00:01 CRDT- 1995/06/01 00:00 PHST- 1995/06/01 00:00 [pubmed] PHST- 1995/06/01 00:01 [medline] PHST- 1995/06/01 00:00 [entrez] AID - 10.1242/dev.121.6.1669 [doi] PST - ppublish SO - Development. 1995 Jun;121(6):1669-80. doi: 10.1242/dev.121.6.1669.