A series of ENU-induced single-base substitutions in a long-range cis-element altering Sonic hedgehog expression in the developing mouse limb bud

AbstractMammal–fish-conserved-sequence 1 (MFCS1) is a highly conserved sequence that acts as a limb-specific cis-acting regulator of Sonic hedgehog (Shh) expression, residing 1 Mb away from the Shh coding sequence in mouse. Using gene-driven screening of an ENU-mutagenized mouse archive, we obtained mice with three new point mutations in MFCS1: M101116, M101117, and M101192. Phenotype analysis revealed that M101116 mice exhibit preaxial polydactyly and ectopic Shh expression at the anterior margin of the limb buds like a previously identified mutant, M100081. In contrast, M101117 and M101192 show no marked abnormalities in limb morphology. Furthermore, transgenic analysis revealed that the M101116 and M100081 sequences drive ectopic reporter gene expression at the anterior margin of the limb bud, in addition to the normal posterior expression. Such ectopic expression was not observed in the embryos carrying a reporter transgene driven by M101117. These results suggest that M101116 and M100081 affect the negative regulatory activity of MFCS1, which suppresses anterior Shh expression in developing limb buds. Thus, this study shows that gene-driven screening for ENU-induced mutations is an effective approach for exploring the function of conserved, noncoding sequences and potential cis-regulatory elements

Magma Ocean, Water, and the Early Atmosphere of Venus

The current state and surface conditions of the Earth and its twin planet Venus are drastically different. Whether these differences are directly inherited from the earliest stages of planetary evolution, when the interior was molten, or arose later during the long-term evolution is still unclear. Yet, it is clear that water, its abundance, state, and distribution between the different planetary reservoirs, which are intimately related to the solidification and outgassing of the early magma ocean, are key components regarding past and present-day habitability, planetary evolution, and the different pathways leading to various surface conditions. In this chapter we start by reviewing the outcomes of the accretion sequence, with particular emphasis on the sources and timing of water delivery in light of available constraints, and the initial thermal state of Venus at the end of the main accretion. Then, we detail the processes at play during the early thermo-chemical evolution of molten terrestrial planets, and how they can affect the abundance and distribution of water within the different planetary reservoirs. Namely, we focus on the magma ocean cooling, solidification, and concurrent formation of the outgassed atmosphere. Accounting for the possible range of parameters for early Venus and based on the mechanisms and feedbacks described, we provide an overview of the likely evolutionary pathways leading to diverse surface conditions, from a temperate to a hellish early Venus. The implications of the resulting surface conditions and habitability are discussed in the context of the subsequent long-term interior and atmospheric evolution. Future research directions and observations are proposed to constrain the different scenarios in order to reconcile Venus' early evolution with its current state, while deciphering which path it followed