CPS49-induced neurotoxicity does not cause limb patterning anomalies in developing chicken embryos

Chris Mahony, Scott McMenemy, Alexandra J Rafipay, Shaunna-Leigh Beedie, Lucas Rosa Fraga, Michael Gutschow, William D. Figg, Lynda Erskine, Neil Vargesson* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
8 Downloads (Pure)


Thalidomide notoriously caused severe birth defects, particularly to the limbs, in those exposed in utero following maternal use of the drug to treat morning sickness. How the drug caused these birth defects remains unclear. Many theories have been proposed including actions on the forming blood vessels. However, thalidomide survivors also have altered nerve patterns and the drug is known for its neurotoxic actions in adults following prolonged use. We have previously shown that CPS49, an anti-angiogenic analog of thalidomide, causes a range of limb malformations in a time-sensitive manner in chicken embryos. Here we investigated whether CPS49 also is neurotoxic and whether effects on nerve development impact upon limb development. We found that CPS49 is neurotoxic, just like thalidomide, and can cause some neuronal loss late developing chicken limbs, but only when the limb is already innervated. However, CPS49 exposure does not cause defects in limb size when added to late developing chicken limbs. In contrast, in early limb buds which are not innervated, CPS49 exposure affects limb area significantly. To investigate in more detail the role of neurotoxicity and its impact on chicken limb development we inhibited nerve innervation at a range of developmental timepoints through using β-bungarotoxin. We found that neuronal inhibition or ablation before, during or after limb outgrowth and innervation does not result in obvious limb cartilage patterning or number changes. We conclude that while CPS49 is neurotoxic, given the late innervation of the developing limb, and that neuronal inhibition/ablation throughout limb development does not cause similar limb patterning anomalies to those seen in thalidomide survivors, nerve defects are not the primary underlying cause of the severe limb patterning defects induced by CPS49/thalidomide.
Original languageEnglish
Pages (from-to)568-574
Number of pages7
JournalJournal of Anatomy
Issue number4
Early online date10 Oct 2017
Publication statusPublished - 1 Mar 2018

Bibliographical note

The authors thank Elizabeth Kilby and Susan Reijntes for preliminary studies. CM was funded by a University of Aberdeen PhD studentship; AJR (née Diamond) was
funded through a BBSRC EastBio DTP PhD Award; S-L B was funded by a Wellcome Trust/NIH PhD Studentship; SM was funded by a Siddall PhD Scholarship
Award; LRF was funded by the Science Without Borders PhD Scheme.


  • thalidomide embryopathy
  • β-bungarotoxin
  • neurite growth
  • retinal explants
  • thalidomide analog


Dive into the research topics of 'CPS49-induced neurotoxicity does not cause limb patterning anomalies in developing chicken embryos'. Together they form a unique fingerprint.

Cite this