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Transient absence of CD44 expression and delay in development by anti-CD44 treatment during ontogeny: a surrogate of
M Zöller1, K Herrmann, S Büchner
1Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany. M.Zoeller@DKFZ-Heidelberg.DE
Abstract:
Because the lack of some adhesion molecules induced by site-directed mutagenesis has been described to be lethal, whereas the lack of others apparently has no effect, we were interested in seeing whether the developing organism might gradually adapt to the absence of adhesion molecules. Therefore, we chose a form of transient interference by i.v. injection of antibody into pregnant rats. As a model, we selected CD44, which has been reported to play a key role during embryogenesis. Rats received either an antibody recognizing an epitope on the CD44 standard isoform (CD44s) or on exon v6 (CD44v6). In the presence of anti-CD44s, delivery was frequently delayed, and intrauterine abortions were often observed. The fetuses were smaller, particularly the anlage of the hair follicle of the whisker, and the formation of alveoli in the lung, of the tubular system of the kidney, and of villi in the gut was delayed. The development of fetuses receiving anti-CD44v6 was hampered until days 16-18 of gestation. Immunodetection revealed a weaker expression of the target molecules at the implantation site and the complete absence of CD44s and CD44v6 expression in fetal tissue until day 12. During the late stages of gestation, the expression pattern of CD44 resembled that of 2-3-day-younger fetuses of untreated rats. Interestingly, degradation of hyaluronate was also delayed, particularly in the kidney. Thus, the diaplacental antibody passage was very efficient and should make it possible to obtain a clearly defined and differentiated concept of the requirements for the CD44 molecule during ontogeny and also for fail-safe mechanisms. Both experiences may be missed in the knockout proper.
Insights
Transiently blocking CD44 adhesion molecules in pregnant rats delayed fetal development and altered organogenesis, revealing CD44
Area of Science:
- Developmental Biology
- Molecular Biology
- Immunology
Background:
- Adhesion molecules are crucial for embryogenesis, but their absence can be lethal.
- The developing organism's ability to adapt to the absence of adhesion molecules is unknown.
- CD44 is a key adhesion molecule implicated in embryogenesis.
Purpose of the Study:
- To investigate the role of CD44 standard isoform (CD44s) and CD44 variant 6 (CD44v6) during rat embryogenesis.
- To determine if transient interference with CD44 function impacts fetal development.
- To understand the adaptive mechanisms of developing organisms to the absence of adhesion molecules.
Main Methods:
- Intravenous injection of antibodies targeting CD44s or CD44v6 into pregnant rats.
- Monitoring of fetal development, including size, organogenesis, and survival rates.
- Immunodetection to assess CD44 expression and hyaluronate degradation in fetal tissues.
Main Results:
- Anti-CD44s treatment led to delayed delivery, intrauterine abortions, and smaller fetuses with delayed organ development (hair follicles, lungs, kidneys, gut).
- Anti-CD44v6 treatment hampered fetal development until days 16-18 of gestation.
- Transient CD44 blockade resulted in reduced CD44 expression and delayed hyaluronate degradation, with fetal CD44 patterns resembling younger controls.
Conclusions:
- Transient interference with CD44 function significantly impacts rat embryogenesis and organ development.
- The study demonstrates the critical role of CD44s and CD44v6 in normal fetal development.
- Diaplacental antibody transfer is effective, providing insights into CD44 requirements during ontogeny that may be missed in knockout models.