Organismal Dynamics

Nuclear Dynamics in Cell and Developmental Biology

Dr Peter Askjaer

 Principal Investigator

Summary 

The nuclear envelope serves to protect and regulate the cell’s genetic material, the chromosomes, inside the cell nucleus. Interactions between chromosomes and proteins at the nuclear envelope are important for correct organization of chromosomes and gene transcription in a tissue-specific manner: although all cells in the body contain the same genes, they express different subsets of them and at different levels.

Our group at the Andalusian Centre for Developmental Biology studies the role of the nuclear envelope in these processes. We are interested in understanding the links between nuclear organization, development, diseases and aging. The nuclear envelope consists of the nuclear lamina, the outer and inner nuclear membranes and nuclear pore complexes that enable communication between the nucleus and the rest of the cell.

 

 

We have identified multiple nuclear pore proteins (nucleoporins) as regulators of nuclear envelope formation, and we have linked several nucleoporins to the mitotic spindle apparatus that is responsible for segregation of the chromosomes to the daughter cells during cell division. Searching for proteins involved in nuclear envelope breakdown, we also identified the protein kinase VRK1 as an essential regulator of nuclear envelope dynamics and demonstrated that it controls interactions between chromosomes and the nuclear envelope.

Proper gene expression correlates often with positioning of chromosomes within the nucleus. Interactions between chromosomes and proteins at the nuclear envelope is important for correct chromatin organization and gene transcription in a tissue-specific manner. For instance, we identified two histone H3 lysine 9 (H3K9) methyl transferases as being responsible for recruitment of heterochromatin to the nuclear periphery in embryonic cells, whereas a H3K36-binding protein is required in differentiated cells. Moreover, we found that the nuclear envelope proteins emerin is specifically involved in both chromatin organization and regulation of neuromuscular junction activity, which may contribute to Emery-Dreifuss muscular dystrophy in humans.

Finally, we are interested in understanding the links between nuclear organization and aging. We have described how nuclear morphology becomes highly irregular in old individuals of the model organism Caenorhabditis elegans, which is reminiscent of the changes observed in humans suffering from progeria syndromes. We discovered that a mutation in Barrier to Autointegration Factor (BAF) affects gene expression and how this may induce premature aging. Importantly, we identified several genes as potential drug targets for future studies.

Five relevant publications 

 

  • Romero-Bueno R, Fragoso-Luna A, Ayuso C, Mellmann N, Kavsek A, Riedel CG, Ward JD, Askjaer P. (2024) A human progeria-associated BAF-1 mutation modulates gene expression and accelerates aging in C. elegans. EMBO J, doi: 10.1038/s44318-024-00261-8.
  • Nkombo Nkoula S, Velez-Aguilera G, Ossareh-Nazari B, Van Hove L, Ayuso C, Legros V, Chevreux G, Thomas L, Seydoux G, Askjaer P, Pintard L. (2023) Mechanisms of nuclear pore complex disassembly by the mitotic Polo-like kinase 1 (PLK-1) in C. elegans embryos. Sci Adv, doi: 10.1126/sciadv.adf7826.
  • Fragoso-Luna A, Romero-Bueno R, Eibl M, Ayuso C, Muñoz-Jiménez C, Benes V, Cases I, Askjaer P. (2023) Expanded FLP toolbox for spatiotemporal protein degradation and transcriptomic profiling in Caenorhabditis elegans. Genetics, doi: 10.1093/genetics/iyac166.
  • Thomas L, Taleb Ismail B, Askjaer P, Seydoux G. (2023) Nucleoporin foci are stress-sensitive condensates dispensable for C. elegans nuclear pore assembly. EMBO J, doi: 10.15252/embj.2022112987.
  • Cabianca DS, Muñoz-Jiménez C, Kalck V, Gaidatzis D, Padeken J, Seeber A, Askjaer P, Gasser SM. (2019) Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nuclei. Nature, 569, 734-9.

Lab members & Collaborators

Lab members

Group leader

Dr Peter Askjaer, pask@upo.es

PhD students

Raquel Romero Bueno
Patricia de la Cruz Ruiz
Paula Monterrubio Asensio

Research assistant

Cristina Ayuso García

Undergrad students

Laura Garzón
Sara Castaño Díaz
Nina Mellmann

Contacts

Office: +34 954 348 396
Lab: +34 954 348 557

Former lab members

Dr Elke PF Klerkx
Dr Pilar Alarcón González
Dr Eduardo Ródenas Martínez
Dr María Jesús Rodríguez Palero
Dr Cristina González Aguilera
Dr Adela María Morales Martínez
Dr Georgina Gómez Saldivar
Dr Agnieszka Dobrzynska
Dr Celia Muñoz Jiménez

 

Collaborators

Dr Marta Artal-Sanz (CABD)
Dr Julien Dumont (JM, Paris, F)
Dr Anita Fernandez (Uni Fairfield, CN, USA)
Dr Susan Gasser (FMI, Basel, CH)
Dr Peter Meister (Uni Bern, CH)
Dr Antonio Miranda-Vizuete (IBIS, Seville, ES)
Dr Manuel J. Muñoz (CABD)

 

Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI)

 

We form part of the group BIO295 – Mechanisms of Animal Development

FLP-Based Toolkit for Spatiotemporal Control of Gene Expression 

 Strains carrying single-copy transgenes expressing codon-optimised FLP 

 

Promoter Cell Type Strain Reference CGC
ckb-3 Somatic gonad BN854 Fragoso-Luna et al Yes
ceh-60 Multiple BN813 Van de Walle et al No
dat-1 Dopaminergic neurons BN617 Muñoz-Jiménez et al Yes
dpy-7 Hypodermal BN550 Muñoz-Jiménez et al Yes
eat-4 Glutamatergic neurons BN993 Rossi et al No
elt-2 Intestine* BN528 Muñoz-Jiménez et al Yes
gpa-14 Neurons BN1205 Fragoso-Luna et al No
hlh-8 M lineage BN502 Muñoz-Jiménez et al Yes
hlh-12 Distal tip cell BN1204 Fragoso-Luna et al Yes
hsp-16.41 Ubiquitous BN646 Muñoz-Jiménez et al Yes
lag-2 Multiple BN558 Muñoz-Jiménez et al Yes
lin-31 Multiple BN1023 Fragoso-Luna et al Yes
mec-7 Mechanosensory neurons BN498 Muñoz-Jiménez et al Yes
mex-5 Germ line BN711 Macias-Leon & Askjaer Yes
myo-2 Pharyngeal muscle BN543 Muñoz-Jiménez et al Yes
myo-3 Body wall muscle BN503 Muñoz-Jiménez et al Yes
nhr-82 Seam cell lineage BN455 Muñoz-Jiménez et al Yes
nhx-2 Intestine BN999 Fragoso-Luna et al Yes
rgef-1 Pan-neuronal BN507 Muñoz-Jiménez et al Yes
tph-1 Serotonin-producing neurons BN499 Muñoz-Jiménez et al Yes
UAS Gal4-compatible BN908 Ayuso & Askjaer Yes
unc-17 Cholinergic neurons BN1133 Fragoso-Luna et al No
unc-47 GABAergic motor neurons BN544 Muñoz-Jiménez et al Yes
unc-122 Coelomocytes BN1029 Fragoso-Luna et al Yes
ACEL-pes-10 Anchor cell AH5957 Spiri et al No

 

* Note that recombination is also detected in the somatic gonad (see panels M-N below); this is not observed when the nhx-2 promoter is used to express FLP.

 

Ayuso & Askjaer. doi: 10.17912/MICROPUB.BIOLOGY.000089
Fragoso-Luna et al. doi: 10.1101/2021.12.21.473632
Macias-Leon & Askjaer. doi: 10.17912/W2G66S
Muñoz-Jiménez et al. doi: 10.1534/genetics.117.201012
Rossi et al. doi: 10.1016/j.cub.2025.03.039
Spiri et al. doi: 10.1242/dev.199900
Van de Walle et al. doi: 10.1371/journal.pone.0242939

 

  

 Figure 3 from Muñoz-Jiménez et al. Tissue-specific FLPase activity. Transgenic animals expressing FLP D5 in specific cell types and the dual color reporter were observed by live confocal microscopy. (A-B) Promoter of rgef-1 (Prgef-1); projection of eight confocal sections (A; adult head lateral view) or single confocal section (B; adult tail lateral view). (C) Pdat-1; projection of four confocal sections of head of L4 larva. Note that the green channel represents co-expressed GFP::HIS-58 and mNeonGreen in this strain (see Supplementary Figure 3). (D-E) Ptph-1; projection of three confocal sections (D; adult head lateral view) or a single confocal section (E; adult vulva lateral view). (F) Pmec-7; projection of seven confocal sections of head of L4 larva. To ease visualization of the weak GFP signal the corresponding DIC image was not included in the merge. Asterisks indicate six unidentified neurons, whereas a seventh neuron might be FLPL. (G-H) Punc-47; late L1; projection of four confocal sections (G; head lateral view) or stitch of single confocal sections (H). (I-K) Phlh-8; single confocal section (I; adult vulva lateral view) or max projections (J; vulva region; eight confocal sections, K; posterior gonad loop region; fifteen confocal sections). Examples of body wall muscle (bwm), coelomocyte (cc), uterine muscle (um) and vulval muscle (vm) cells are indicated. (L-N) Pelt-2; L1 (L; projection of seven confocal sections) and L2 larvae (M; projection of seven confocal sections, N; single confocal section corresponding to boxed area in M; note weak GFP expression in the gonad primordium [*]). (O-P) Pmyo-3; projection of seven confocal sections of L2 (O) and L4 (P) larvae. (Q) Pmyo-2; projection of twelve confocal sections of adult head. (R-T) Pdpy-7; projection of eight (R; head lateral view) or ten (S; vulva lateral view) confocal sections of L4 larva or single confocal section of L3 larva (T). Examples of vulva cells (vul) and ventral nerve cord neurons (VNC) are indicated. Arrow points to intestinal cell that expresses both markers. (U) Pnhr-82; projection of four confocal sections of tail of young adult. Note that white nuclei indicate simultaneous expression of mCh::HIS-58 and GFP::HIS-58. (V-W). Plag-2; projection of six confocal sections (V) or single confocal section (W) of central region of young adult. Spermatheca (sp) and distal tip cell (DTC) are indicated. All micrographs are oriented with anterior to the left and ventral down. Scale bar 10 µm.