Stage-specific homeotic vertebral transformations in mouse fetuses induced by maternal hyperthermia during somitogenesis

Abstract

To investigate the heat shock effects upon somitogenesis and specification of the vertebral identity, pregnant ICR mice were briefly exposed to 42°C or 43°C at E7.5, E8.5, or E9.5 (noon of the plug day = E0.5). Heat treatment induced embryonic day‐specific vertebral transformations whose frequency and severity were dependent on the temperature elevation. Following a heat treatment at E8.5, the vertebral identity of T6 through S1 was shifted anteriorly by one or two segments (posterior transformations). Such shifts were found in more than one‐third of the fetuses heat‐stressed at 42°C, and in over 90% of those exposed to 43°C. When heated at E7.5, the anterior boundary of vertebral transformations was shifted cranially to cervical levels (C1–C7), and when heated at E9.5, it was shifted caudally to the lower thoracic and lumbar levels (T13–L4). Examination of Hox gene expression domains by in situhybridization showed that the anterior boundaries of Hoxa‐5, Hoxa‐7, Hoxc‐8, and Hoxc‐9 expression domains in the paraxial mesoderm were shifted cranially by one somite segment in embryos heated at E7.5, as compared with the corresponding levels of their expression in control embryos. Such cranial shifts were found for Hoxa‐7, Hoxc‐8 and Hoxc‐9, but not for Hoxa‐5, in embryos heated at E8.0. In embryos heated at E8.5, only the expression domains for Hoxc‐8 and Hoxc‐9 were found to be shifted. The observed stage‐specific vertebral transformations and shifts of the Hox gene expression domains were consistent with the temporal colinearity and posterior predominance of Hox gene expression during development. Further histological and cytochemical analyses revealed that heat‐induced vertebral transformations may not be a result of induced cell death, but heat‐induced transient arrest of cell proliferation and somitogenesis could result in altered expression of Hox genes and subsequently produce vertebral transformations. Dev Dyn 1999;216:336–348. ©1999 Wiley‐Liss, Inc.

Heat shock during early somitogenesis induces caudal vertebral column defects in Atlantic salmon (Salmo salar)

“…7a). In agreement with this, HS in mice and rats inhibits cell proliferation, leading to vertebral deformity (Breen et al 1999;Li and Shiota 1999). In mice, more than 4,000 genes are transcriptionally altered after HS, indicating that our study of two genes reflects "a short chapter" of the whole story (Mikheeva et al 2004).…”

Extraordinary incidence of cervical ribs indicates vulnerable condition in Late Pleistocene mammoths

“…Recent studies have shown that the genetic diversity was extremely low in Late Pleistocene mammoth populations in Siberia (Miller et al, 2008; Nyström et al, 2012). Additionally, the increased incidence of cervical ribs may be due to harsh conditions that impact early pregnancies, because diseases, famine, cold and other stressors can lead to disturbances of early organogenesis, that can result in the induction of cervical ribs (e.g., Sawin, 1937; Li & Shiota, 2000; Wéry et al, 2003; Chernoff & Rogers, 2004; Steigenga et al, 2006). Harsh conditions during the Late Pleistocene, a period of intense climatic fluctuations and ecosystem instability, are plausible (Brace et al, 2012).…”

“…Despite the extreme evolutionary conservation of the number of cervical vertebrae, intraspecific variation is not uncommon in mammals. The most common variation is represented by ribs on the seventh vertebra, so-called cervical ribs, which can be considered a partial or complete homeotic transformation of a cervical into a thoracic vertebra (involving a change in the activity of Hox genes (Galis, 1999; Li & Shiota, 2000; Varela-Lasheras et al, 2011; Wéry et al, 2003)). The strong conservation of the number of cervical vertebrae implies that there must be selection against intraspecific variation of this number.…”

“…In other mammalian species, we have also found an association with abnormalities (Varela-Lasheras et al, 2011). A cervical rib itself is relatively harmless, but its development is induced by a (genetic or environmental) disturbance of early embryogenesis (Li & Shiota, 2000; Wéry et al, 2003; Chernoff & Rogers, 2004; Galis et al, 2006). Such a disturbance usually has multiple effects, due to the highly interactive nature of early embryogenesis.…”

Understanding the somitogenesis clock: What’s missing?

“…Heat shocks were proposed to affect somite delimitation by the 'prior wave'. Disruption of somitogenesis by heat shocks is a phenomenon shared (with some differences) across species; the first defects occur after 6-7 somites in chick , 4-5 somites in zebrafish (Roy et al, 1999), 4 somites in rats (Cuff et al, 1993), but less than 2 somites in mouse (Li and Shiota, 1999).…”