We have generated a series of Erbb2 cDNA knock-in animals to explore the role of signaling pathways coupled to Erbb2 during development. Although this knock-in allele was hypomorphic, expressing tenfold less Erbb2 protein than wild type, the knock-in animals were healthy. However, a further twofold reduction in Erbb2 levels in hemizygous knock-in animals resulted in perinatal lethality with defects in the innervation of the diaphragm. Genetic rescue of this hypomorph was accomplished by expression of the Erbb2-Y1028F mutant in a comparable knock-in allele. Interestingly, hemizygous Y1028F animals were viable with normal innervation of the diaphragm. Molecular analyses revealed that the Y1028F allele expressed higher levels of Erbb2 and that Y1028 promoted the turnover of the receptor. In addition, ablation of the Shc-binding site in Erbb2 (Y1227) resulted in subtle defects in the sensory nerves not observed in the other mutant erbb2 strains. Thus, we have established how Erbb2 levels may be modulated through development and that a minimum threshold level of Erbb2 is required.
History of our journals
As our publisher, The Company of Biologists, turns 100 years old, read about Development’s journey and highlights from some its first issues, and explore the history of each of our sister journals: Journal of Cell Science, Journal of Experimental Biology, Disease Models & Mechanisms and Biology Open.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues
Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology
In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
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